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A CHEAP drug that鈥檚 been on the market for almost 40 years could build bone mass in post-menopausal women, providing an alternative to hormone replacement therapy for preventing osteoporosis.

Two years ago Gerard Karsenty鈥檚 team at the Baylor College of Medicine in Houston showed that a hormone called leptin stops new bone forming in mice. But leptin is best known for its role in appetite and fat metabolism. If you tried to boost bone growth by blocking leptin the body would react as if it was starving, demanding more food and shutting down the immune system and reproduction. 鈥淣o one wants to become obese to prevent osteoporosis,鈥� says Karsenty.

If you knew exactly how leptin inhibits bone growth, however, it might be possible to block this specific pathway alone. Karsenty鈥檚 team wondered if the sympathetic nervous system (SNS) 鈥� the 鈥渇ight or flight鈥� mechanism 鈥� was the link between leptin and bone mass, because leptin activates the SNS. Sure enough, they found that drugs that activate the SNS in mice cause bone loss 鈥� without affecting the animals鈥� weight.

Next they tried a drug called propranalol, a beta blocker that inhibits the SNS. Beta blockers have relatively few side effects and have long been used to treat problems such as high blood pressure, because inhibiting the SNS causes blood vessels to relax and dilate. Karsenty鈥檚 team found propranalol increased bone mass, again without causing weight gain (Cell, vol 111, p 305).

The big question is whether the drugs will have the same effect in people, where studies looking at leptin levels and bone density have had mixed results. Indeed, some animal studies suggest leptin actually builds bone. And hopes that leptin itself could work as an appetite suppressant were dashed when human trials showed the process was more complex than thought.

But beta blockers do look promising, as it鈥檚 already known they can prevent bone loss in people with an SNS disorder called reflex sympathetic dystrophy. Karsenty鈥檚 team is now planning trials in people.