, , ,

Boning up on osteoporosis - how hibernating polar bears could yield a new generation of treatments

Boning up on osteoporosis - how hibernating polar bears could yield a new generation of treatments

Disuse osteoporosis is bone loss resulting from reduced mechanical loading of the skeleton; the processes of bone formation and bone resorption,in which cells known as osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood, become unbalanced. This is big problem for those immobilised due to a stroke or spinal cord injury or, in a thoroughly modern problem, those who are so obese that they are either entirely bed-ridden or sedentary for the majority of their lives.

It has recently been elucidated that two species of hibernating bear seem resistant to bone loss by disuse. Investigating their mechanisms of bone preservation could, it is hoped, lead to improved treatments for osteoporosis.


Effects of Disuse on Bone

Bone typically remodels in response to the mechanical loading it experiences. Exercise and over-loading results in an increase in bone mass, whereas disuse results in a decrease in bone mass, structure and strength. This is the result of bone resorption occurring at a greater rate than bone formation and brings about an increased risk of fracture.

Bone Resorption Osteoclasts are very large multinucleated cells that arise from the fusion of macrophages. Osteoclasts attach themselves to the bone matrix and form a tight seal at the rim of the attachment site. Upon activation, they release their digestive contents to break down the collagen fibres that make up the matrix.
Bone ResorptionOsteoclasts are very large multinucleated cells that arise from the fusion of macrophages. Osteoclasts attach themselves to the bone matrix and form a tight seal at the rim of the attachment site. Upon activation, they release their digestive contents to break down the collagen fibres that make up the matrix.


Effects of Disuse in Humans

Bone disuse has a profound effect on the integrity of human bone. In human 120-day bedrest trials, a 30-40% increase in carboxyterminal telopeptide type 1 collagen (ICTP) – a marker of bone resorption – was measured. There was also a significant increase in the amount of calcium in the urine, suggesting marked increases in bone loss.

These remodelling events lead to deleterious alternations in bone structure and geometry:

  • A 17% decrease in bone mineral density after the 1st year of a serious spinal injury and a further 1.5% for every year afterwards.
  • A long-term spinal injury results in a significant decrease in the cross-sectional area and cross-sectional movement by 25-38%
  • Fracture rates double in the 1st year after a serious spinal injury.

In light of these problems it is imperative that the current treatments for disuse osteoporosis are improved. Current treatments are in their majority prophylactic, but also include the administration of nitrogen-containing bisphosphates which inhibit the action of osteoclasts and daily injections of parathyroid hormone (PTH), which regulates serum calcium levels, affecting how the body recycles it and uses it in bone formation. PTH does this by acting on a specific receptor on the surface of osteoclasts to prevent the increased apoptosis and reduced bone formation associated with disuse.

Though these aggressive treatments do alleviate the loss of bone during long periods of disuse, it is hoped that by further understanding the processes that occur in hibernating polar bears, who do not suffer from any loss in bone mass during their three month hibernation, can help bring about a new generation of osteoporosis treatments.


Translating Bone Preservation Mechanisms into Humans

In contrast to smaller mammals, there is evidence that bears actively prevent bone loss during hibernation. What has not been clear, however, is whether these bears protect themselves from the onset of osteoporosis by continually balancing the processes of formation and resorption or whether they allow for a period of resorption and follow it up with enhanced formation. Recent analyses of the levels of the markers of bone formation and resorption in polar bear serum suggest that it is the latter of these processes.

What is thought to be key to this ability to increase the rate of bone formation when required is the polar bear’s form of parathyroid hormone (PTH). Polar bear PTH has a 9 amino acid difference to human PTH. Since other animals respond positively to PTH from other species – rats demonstrate a 37% increase in bone volume when treated with bovine PTH, which has a 5 amino acid difference – it is hoped that new treatments with bear PTH may yet yield a better response than current therapies. Current trials are underway to determine whether recombinant bear PTH – that is, bear PTH which has been produced in large volumes by bacteria who have have the gene engineered into their genome – could be the solution to the relatively poor treatments for disuse osteoporosis used at the moment.

‘Til next time…

Joe

 

One Response

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.