Briefing: The falling dollar

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New Diabetes Drugs Bad for Bones - Avandia -- and Probably Actos -- Speeds Up Bone Loss

The diabetes drug Avandia promotes osteoporosis not only by slowing bone growth but also by speeding up bone loss. Actos, the only other drug in the same class, likely does this as well.

The finding, from mouse experiments by Salk Institute researcher Ronald M. Evans, PhD, and colleagues, helps explain why clinical studies show increased bone fracture risk in people taking Avandia.

Bones stay healthy through an ongoing process called remodeling. The body is constantly breaking down and rebuilding bone. This system of resorption and deposition is tightly controlled with many checks and balances.

"The drug shifts this balance on both sides," Evans tells WebMD. "People taking this drug have somewhat decreased bone deposition -- that is a known action of the drug, resulting in mild bone loss. But what we discovered is it increases bone resorption in a fairly robust way."

Avandia belongs to the glitazone class of drugs, which enhances a chemical signal called PPAR-gamma. One effect of the drug is to increase the body's sensitivity to insulin. But another effect, Evans and colleagues now show, is to activate the bone-eating cells called osteoclasts.

"I would expect to see the same thing with Actos, although we did not actually do that experiment," Evans says. "But it is almost certainly a drug-class effect because the mediator of this effect is the target of both drugs."

Bone Risk From Avandia, Actos

"This is not meant to scare people," Evans asserts. "Only Avandia and Actos act in this unique way, and these drugs are an overall benefit for the patients who take them."

But bone expert J. Edward Puzas, PhD, professor of orthopaedics at the University of Rochester, N.Y., says the new finding confirms something bone researchers have been worrying about.

"This is a nicely done study of how these drugs stimulate the cells that eat away at bone. This leads to lower bone mass and higher bone fragility," Puzas tells WebMD.

Puzas is worried because bone changes occur very slowly, so researchers may only be beginning to appreciate the scope of the problem.

Philip T. Rodgers, PharmD, clinical associate professor of pharmacy at the University of North Carolina, hopes the new findings will make doctors pay more attention to the bone risks posed by Avandia and Actos.

"There is an underappreciation of the risks of osteoporosis with these drugs," Puzas says. "I don't think doctors are paying enough attention to testing the bone-mineral density of people on these drugs."

Mary Anne Rhyne, a spokeswoman for Avandia maker GlaxoSmithKline, says the company is already aware of the drug's bone risks. She notes that the company recently updated the drug's label to reflect new data on fracture risk.

"We have a comprehensive, ongoing clinical program to better understand the mechanism of fractures," Rhyne tells WebMD.

While they worry about the bone risks from Avandia and Actos, both Puzas and Rodgers note that the drugs' benefits outweigh the risks for many patients.

Both suggest that doctors should screen patients for osteoporosis before starting them on Avandia or Actos therapy. And both suggest that patients taking the drugs should discuss bone-protection strategies with their doctors.

Meanwhile, Evans says the new findings should help researchers come up with new diabetes drugs that improve insulin sensitivity without stimulating bone loss.

Evans and colleagues report their findings in this week's advance online issue of Nature Medicine.

SOURCES: Wan, Y. Nature Medicine, published online Dec. 2, 2007. Ronald M. Evans, PhD, professor, Salk Institute for Biological Studies, La Jolla, Calif. J. Edward Puzas, PhD, professor of orthopaedics, University of Rochester, N.Y. Philip T. Rodgers, PharmD, clinical associate professor, University of North Carolina School of Pharmacy; director of pharmacy education, Duke University Medical Center. Mary Anne Rhyne, spokeswoman, GlaxoSmithKline.

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By Daniel J. DeNoon
WebMD Medical News

Reviewed by Louise Chang, MD

China 2007: An intimidating but brittle colossus

The 2008 Olympics has been billed as the biggest coming out party in history, delivering a stage on which China can reclaim recognition as one of the world’s great and powerful nations. But in truth, the Olympics will simply provide a high-grade political gloss for a nation that has already well and truly returned to a position of pivotal global influence.

After nearly three decades of uninterrupted economic expansion, and five straight years of double-digit-plus increases in output, China has become a motor of growth for the global economy and is on the verge of becoming the largest trading nation in the world.

The reconstruction of its cities and the building of new ones to absorb millions of rural migrants each year has translated into a huge demand for resources, lifting global prices for commodities such as copper, nickel and iron ore.

China is also staking its claim to the management and ownership of global resources, striking deals in central Asia, Australia, and, most controversially, in Africa, where state companies have been backed by concessional loans from Chinese development banks.

Chinese technology, telecommunications and shipbuilding industries are striving to compete on the world stage. they are laying the ground for a stronger indigenous military capability, delivering not just the ability to mount a decisive attack on Taiwan, but also, eventually, to project power into south-east Asia and the Indian ocean with a blue-water navy.

Although consumption continues to grow more slowly than investment and exports, China has also become the most promising new market in decades for a host of multinationals – from carmakers to fast-food companies and industrial goods suppliers.

China’s transformation has been backed with a relentless and, for the most part, highly effective diplomacy, which embraces international institutions and global multinationals, even as its tries to leverage them for domestic interests.

Beijing’s position on the United Nations Security Council has ensured that it has become an indispensable, if not always enthusiastic, partner for Washington, carrying messages to North Korea, and to a lesser extent, Burma, and cautiously moving in tandem with the west on issues such as Iran. At the same time, China has been willing to defend robustly its interests in places such as Africa, remaining loyal to the regimes in Sudan and Zimbabwe, despite mounting criticism from many western governments and activists.

Business criticism of Beijing in the US and Europe has been relatively muted, largely because of the huge investments of multinationals in China and the growth they foresee in the market. But the downside of high speed economic growth has seen China set other, less enviable records. Even with an economy that is a quarter to one-fifth the size of the US, China is set to surpass the US this year as the world’s biggest emitter of greenhouse gases, largely because of a surge of investment in capital- and energy-intensive industries since 2000.

The cost of China’s headlong growth is evident across the country in the biting air pollution in the cities, and the factory waste that has damaged agricultural land and rivers. The fruits of China’s growth have also not been evenly shared. China is now more “unequal” than the US and Russia, according to a recent study by the Asian Development Bank. It is a galling achievement for a country that claims to be still “in the early stages of socialism”, and has been identified as a big political problem by Hu Jintao, the president.

Even some statistics cited as signs of strength, such as the country’s bulging foreign exchange reserves, which stood at $1,400bn at the end of August, are increasingly a sign of weakness, and a millstone around the government’s neck.

China’s decision to manage tightly its currency, the renminbi, means it has no choice as to its level of foreign reserves. The dollars coming into the country have to be bought by the central bank to keep the renminbi basically stable.

With the trade surplus running at about $25bn a month, the reserves have been swelling rapidly, and for the most part earning a relatively paltry return in low-yielding securities overseas. Over time, as the US dollar declines, China will inevitably suffer huge losses on reserve holdings.

China’s refusal to allow its currency to appreciate faster remains difficult to fathom. A stronger currency would help damp rising inflation and capital inflows, and provide reduced incentives for exporters – a stated aim of government policy.

But caution, a byword in financial reform, and the need for consensus among powerful ministries, continues to stay the hand of policymakers. So too, according to many critics of the government, does the weakness of Wen Jiabao, the premier, who seems incapable of putting his personal stamp on financial and economic policy.

China is attempting to encourage an outflow of capital, and has also established a sovereign investment agency to chase higher returns for a portion of its reserves, but neither measure will be able to stem the tide of incoming funds for the moment.

All in all, a China that can look intimidatingly powerful from the outside can equally seem dangerously brittle when examined up close.

Senior Chinese officials offer a similar mixture of confidence and trepidation in interviews. Liu Mingkang, chairman of the China Banking Regulatory Commission, has presided over a generational reform of the country’s big state banks, but says “their progress is very initial and sometimes very superficial”.

China’s development model, and the struggle of the government to change it, also puts Beijing on a potential collision course with the US and Europe. The European Union, to which exports have been growing at twice the rate of sales to the US this year, has taken over as China’s largest trading partner.

The current account surplus is set to reach 12 per cent this year, a level unheard of for a country of China’s size and weight in the global economy. Guo Shuqing, a former central bank vice-governor who now heads China Construction Bank, says the problem is not external imbalances, in the form of the current account surplus, but “the internal imbalances”.

“Although it is under-reported in several areas, consumption is too low, particularly in education, medical care and other areas, like financial services,” he says. “Government-financed public services are too small, especially compared with the growth rate.” If the US economy continues to slow, there are few other countries in the world that could make up for the demand that America generates in the world economy. Without China stepping up to the plate, any global downturn would be steeper and longer.

The Chinese supertanker, however, continues to change direction at a frustratingly slow pace, according to not just the benchmarks set by its trading partners, but also those mandated by the central government. Without an acceleration of policy change, a nasty collision may be just over the horizon.

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By Richard McGregor

Published: October 9 2007 08:48 | Last updated: October 9 2007 08:48

Market Scan:"

Market Scan:"

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Adviser SoapboxEnergy Stocks With A Full Tank

David Wright, Upside 08.09.07, 12:16 PM ET