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

Abstract

Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

Figure 1

One femur was used for mechanical testing (A) and processed post-fracture to determine cross-sectional properties (B) and ash fraction (C). Mechanically tested femurs fractured at midshaft below the point of load application. The contralateral femur was used for histological analyses of static and dynamic remodeling indices and quantification of intracortical porosity (D).

Figure 2

The distance between calcein labels (Ir.L.Wi) was quantified for double labeled osteons and was used to calculate the osteonal mineral apposition rate (On.MAR) by dividing Ir.L.Wi by the time between calcein injections. The percentage of the osteon left to be refilled (%W.Wi.UF) was calculated using the outer calcein label (R_o), cement line (Cm.Rd), and Haversian canal radii. The osteonal mineral apposition rate was normalized (On.MARN) by %W.Wi.UF to account for the non-linear refilling rate of osteons.

Figure 3

A: Labeled osteon density was decreased (p = 0.031) in hibernating compared to active bears (40x original magnification). B: There were no differences in labeled osteon density (p > 0.198) between quadrants in either hibernating or active bears.

Figure 4

Resorption cavity density for the active bears was the only remodeling parameter that varied significantly by quadrant. Quadrants with the same letter are not significantly different from each other (p > 0.05). Means with SE bars are presented.

Figure 5

Bone geometry and intracortical porosity do not respond similarly to disuse in turkeys (a, b) and grizzly bears (c, d). A: control turkey ulna, B: turkey ulna immobilized for 8 weeks, C: active grizzly bear femur, D: grizzly bear femur after 17 weeks of hibernation. Large intracortical pores and thinning of the bone cortex, which occur during disuse in the turkey ulna, are not seen in the hibernating grizzly bear femur. In contrast, grizzly bear bone becomes less porous during physical inactivity. Turkey ulnae images are reproduced from: J Biomechanics 17(12), Lanyon, L. E. & Rubin, C. T., “Static vs dynamic loads as an influence on bone remodeling,” pp. 897-905, copyright Elsevier (1984).

Figure 6

Proposed mechanism for how parathyroid hormone (PTH) could decrease cortical bone remodeling in hibernating grizzly bears.