Hibernating Bears (Ursidae)

Metabolic Magicians of Definite Interest for the Nephrologist

Peter Stenvinkel; Alkesh H Jani; Richard J Johnson

Disclosures

Kidney Int. 2013;83(2):207-212. 

In This Article

Preservation of Bone Mass During Hibernation

Osteoporosis with bone loss and increased fracture risk are common features of the uremic phenotype and have been linked with vascular calcification and increased mortality.[54,55] The causes of uremic bone disease are multifactorial and include hyperparathyroidism, vitamin-D insufficiency, prolonged corticosteroid treatment, renal failure–associated hypogonadism, and, in many patients, immobilization. Immobilization for periods between 7 and 27 weeks results in up to 40% cortical bone loss in humans.[56] Moreover, Beller et al.[57] demonstrated regional differences in bone loss in women during prolonged bed rest, with incomplete recovery of this loss even 1 year after bed rest. In addition, other hibernating animals, such as bats[58] and golden hamsters,[59] develop some bone loss. In contrast, McGee-Lawrence et al.[60] reported no difference in bone volume fraction and tissue mineral density between hibernating and active bears. As physical inactivity and reduction in mechanical load leads to loss of bone mass in nonhibernating species, it is surprising that inactive and anuric denning bears show no loss in bone mass and strength and maintain normal calcium levels.[61,62] Studies have shown that hibernating bears have evolved the unique ability to preserve calcium homeostasis completely during hibernation by preventing both cortical[63] and trabecular[60] bone loss.

Although the mechanism(s) that maintain balanced bone remodeling during hibernation remain unknown, bears have likely evolved physiological processes to recycle calcium, prevent hypercalcemia, and maintain bone integrity. As bears appear to excrete minimal amounts of waste products during their anuric hibernation period, calcium released from bone is likely recycled back into the skeleton.[64] It has been proposed that, in analogy with the situation in uremia, the skeleton of hibernating bears is adynamic.[65] However, lactation and pregnancy (which both may occur during hibernation) require active bone formation, and Seger et al.[66] recently demonstrated that the skeleton of a hibernating bear is neither in a high-turnover state nor in an adynamic state.

Among several proposed mechanisms by which bone loss is prevented during hibernation, the effects of black bear parathyroid hormone (bPTH) has attracted interest, which positively correlates to bone formation markers during hibernation, increases survival signals in osteoclastic cells, and stimulates osteoblastic activity.[63,67] A rise in bPTH during hibernation has been proposed to conserve calcium by increasing renal tubular calcium reabsorption.[67] The potential of bPTH as a novel treatment strategy in osteoporotic conditions was recently tested in a model of dystrophin-deficient mice.[68] Recombinant bPTH was found to have a greater anabolic effect and increased bone volume fraction to a greater degree than human PTH. Thus, further studies should be conducted to test whether this intriguing bear peptide could be used for the treatment of human osteoporotic conditions.[68]

To obtain insights about the molecular mechanisms that prevent bone loss during hibernation, Fedorov et al.[69] recently conducted a large-scale screening of transcriptional changes in trabecular bone in nonhibernating and hibernating winter bears. They found that apoptosis genes were downregulated during hibernation, whereas the expression of anabolic genes was increased.[69] Changes in vitamin-D metabolism might be another mechanism to preserve bone mass in hibernating bears. Vestergaard et al.[62] demonstrated marked changes in vitamin-D3/D2 ratio between hibernating and summer-active Swedish brown bears. Moreover, 25(OH) vitamin-D levels are significantly higher in hibernating bears,[62] and despite anuria 1,25(OH)2 vitamin-D is produced in bear kidneys.[66] This contrasts with humans in whom there is a close correlation between renal function and vitamin-D levels.[70] Other mechanisms by which hibernating bears may prevent bone loss include a role for lower serotonin levels and altered neuroendocrine control of bone remodeling.[60,66] Seger et al.,[66] for example, recently demonstrated that hibernation in bears represents a unique model in which suppression of sympathetic activity prevents bone loss by influencing the inhibitory effects of leptin on bone formation via central hypothalamic effects.[71]

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