Density counts: Duchess Camilla visits a Osteoporosis Centre in Southampton, UK

Osteoporosis is a serious and costly disease. It is also a silent disease ? silent, that is, until a bone breaks in response to a relatively minor stress, like tripping on a step. Several drugs in the bisphosphonate class ? Fosamax and Actonel taken weekly and Boniva taken monthly ? have been shown to stem further bone loss, increase bone density and cut fracture rates in half in women with established osteoporosis. The same effect has been seen in women with somewhat less bone loss who, for other reasons, are at high risk for a fracture.

But what about the many postmenopausal women with a lesser degree of bone loss called osteopenia? Should they, too, take a bisphosphonate to protect their bones after meno-pause? Is this cost-effective, and is it likely to help the women more than it harms them? Specialists across the US are divided in their answers. Nearly all the experts, pro and con, act as consultants or receive research grants from the companies that make the bone-protecting drugs.

Most experts say the inevitable loss of bone after menopause and the proven ability of these drugs to prevent fractures clearly outweigh the risks stemming from a slowdown in bone renewal. But others fear that long-term use of bisphosphonates can render bones more brittle and more likely to break, even as they increase bone density.

Dr Susan M. Ott, a bone expert at the University of Washington, said studies suggested that old bone that was not renewed lost its elasticity. She likened it to the effects of a very strong wind on a young tree versus a thicker old one. Young trees bend under the stress without breaking; older ones, though denser, are more likely to snap in two.

Fracture risk, said Dr Michael R. McClung of the Oregon Osteoporosis Center in Portland, is complex, and the diagnosis of osteopenia and treatment with bisphosphonates should not be based on bone mineral density (BMD) tests alone. It is clear, McClung wrote in May in the Annals of Internal Medicine in response to a report on cost effectiveness, “that pharmacologic therapy is not cost-effective in women selected solely on the BMD diagnosis of osteopenia.”

What follows should not scare women away from bone-sparing drugs if they are at high risk for fractures because of thinning bones. But before every woman found to be osteopenic on a density test is advised to take a bisphosphonate, it may be wise to consider some early warning signs of possible harm to the architecture of bones after many years on such drugs.

Though bones appear to be solid, they are fluid structures that are continually remodelled ? broken down by cells called osteoclasts and rebuilt by cells called osteoblasts. When a bone is injured ? and injuries called microcracks occur all the time from ordinary stress ? bone-resorbing osteoclasts have to remove the damage so that the bone-building osteoblasts can fix it.

Bisphosphonates increase bone density by adding minerals to bones. But they are potent inhibitors of bone resorption, drastically slowing bone remodelling. In The Journal of Clinical Endocrinology & Metabolism last March, Ott noted that “after prolonged severe suppression of bone formation, bone could become too brittle and/or accumulate microdamage,” which has been shown to occur in animals given high doses of bisphosphonates. Such damage “could eventually weaken the bone” and result in fractures after minor stresses. A report in the same journal described nine patients on Fosamax with osteoporosis or osteopenia who had nontraumatic fractures.

Six patients continuing the drug experienced delayed or no healing of broken bones. The authors said that Fosamax might impair bone healing and that the drug-induced increase in bone minerals could make bones more brittle.

The published cases mimic that of a healthy active woman, 59, who after six years on Fosamax for osteopenia in her spine was jolted on a subway and broke her thigh bone. The injury took two years to heal, and the healing occurred only after she had stopped taking Fosamax. A year later, she resumed the drug, only to suffer a nontraumatic fracture in her foot. Dr Joseph M. Lane, an orthopedic surgeon in New York, described eight other patients who had fractures of the femur, many of them described as hard to heal. All the patients had been on Fosamax for more than five years.

While it’s not possible to know in any of these cases whether the unusual fractures and delayed healing resulted from Fosamax or patients’ existing bone disease, the researchers noted that bone biopsies disclosed “marked suppression of bone turnover,” which can render bones more brittle and delay repairs.

On the other hand, Lane noted, the drugs clearly preserve the microarchitecture of bones that is otherwise lost in the first few years after menopause, and a long-term Canadian study found a lower than expected rate of hip fractures among women on the drugs.

Further, Dr Robert Recker, an endocrinologist at Creighton University in Omaha, said his bone biopsy studies showed that osteoporotic women taking Fosamax remodelled bone at rates comparable to those of healthy premenopausal women. This finding left him unconcerned about the suppression of bone turnover on Fosamax because premenopausal women rarely suffer nontraumatic fractures.

NYTNS