Move over milk... Merck is so determined to help your grandma maintain strong bones that you won't believe the lengths they've gone.
With our female family members nearing retirement age, I am sure you've seen a bottle of calcium supplements or other bone-promoting medications on their kitchen table. Clearly osteoporosis is a health concern (especially for women, who lose bone more rapidly than men due to hormone changes after menopause), and we all know of a senior citizen whose quality of life was really impacted by broken bones from a fall (even 1 in 5 elderly women will die a year after a broken hip, due to other health complications associated with their disability). In the last decade or two, new specialty drugs have emerged that proactively reduce the chance of osteoporosis, and have blossomed into a multi-billion-dollar industry (since the trick with preventative drugs is you never know if you'll truly be at risk, so you better take them for the rest of your life to be safe).
Obviously osteoporosis doesn't occur overnight; there is a gradual loss of bone tissue, like how mild senility precedes dementia and Alzheimer's. So the "onset" of osteoporosis is named osteopenia, or bone thinning. But like senility, humans lose bone mass normally with age. So when is bone loss pathological? When do women reach the osteopenia zone (I'll refer to it as OP from now on)? Well, the cutoff point was literally decided arbitrarily by a room of bone experts at a WHO summit (they drew a line on a graph and that settled it). Unfortunately, many human diseases are not understood and merely classified by a set of symptoms that reach an arbitrary degree of severity, with clinical depression being an obvious example. Getting back to OP, the "disease" was decided to apply to people who were hovering near the osteoporosis cutoff.
Merck happened to have a bisphosphonate drug (later marketed as Fosamax) that inhibits the cells that digest bone. So without those cells' normal or pathological activity, osteoporotic people will lose bone slower. The problem is that bone is like a highway. It needs to be maintained and repaved occasionally from all the wear and tear. Those cells don't eat bone to be mean. They clear out old or weakened bone so other cells can lay down new, stronger bone. The renewing miracle of life. And the bone-laying cells do so very messily, like a kid with paint. The bone-eating cells are critical to remodel the bone, repair micro-cracks, and make it more structurally sound. Addition by subtraction. So actually a femur with more bone mass may be weaker than a thinner femur that is remodeled correctly by the bone-eating cells. So it's good that Fosamax stops over-active bone-eating cells from making a person's bones dangerously thin, but then over time the patient also loses some ability to maintain the strength in their bones through normal remodeling. In addition, Fosamax-type drugs are implicated in dozens of side-effects, and over 400 lawsuits were filed against Merck for the disease ONJ (in brief, wasting away of the jaw due to inability of that bone to heal after dental work, etc.).
But no bother, Merck wanted to sell Fosamax to the droves of aging people who were living longer, and would need to pop these pills for decades. Their major problem was people weren't using Fosamax, because they weren't getting diagnosed with osteoporosis until after they'd had an accident and doctors could examine their bones. Old people get more frail and reduce their activities. No one thinks that could be the sign of disease. Whole-body DEXA bone scans did exist in the 1990s, but they were costly ($200-300, and not covered by insurance) and there weren't many clinics that had the bulky pool-table-sized devices (~200 in the entire US). So Merck hired a team of consultants to fix the dismal situation. Bone scanners would be in every town, and older people would get scanned often (if they were successful).
So Merck set up a shell nonprofit called the Bone Measurement Institute (that employed an entire one person), and some top orthopedists became affiliated. They pushed doctors to use a peripheral, portable bone scanner that measured forearm or heel bone density, in order to extrapolate that to spine and hip bones (the bones that, if broken, would cause the most trouble for an osteoporotic patient). But doctors were hesitant: bone is highly dynamic and responds to the specific local loads upon it, and a vertebra is a lot different than a mandible (so you can't know the weather in London by looking out your window in Paris). The manufacturers of the traditional bone scanners were irate about this new competition in their niche market. Since they sold few traditional scanners per year, they needed to make them very expensive to recover costs. When Merck's portable scanner project didn't pan out, they decided to buy a traditional bone scanning company instead. Merck then slashed the cost of traditional scanners, forcing competitors to do the same or go out of business (and some did). So Merck won two-fold: they got revenge on the scanner companies who obstructed them, and cut the cost of scanners to facilitate their dissemination across the country (and reduce the scan costs to patients, making it more likely that they would seek one). They closed their scanner company soon afterward.
Merck funded clinical trials and submissions to the FDA to also get the peripheral scanners approved as diagnostic tools. They literally went door-to-door and even organized leases with doctors. Such measures to get more patients on their drug. Just imagine if they invested all that effort and resources into science, to actually understand human diseases better and design drugs more intelligently. But they're not a charity after all. Though of course better drugs will sell themselves and cost the company less in failed multi-million-dollar clinical trials and litigation. Anyway, Merck didn't stop there. They funded some third-party org's to lobby Congress to pass the Bone Mass Measurement Act in 1997, which made bone scans eligible for Medicare reimbursement (and some private insurance did the same). Now pay-for-service physicians could make good money on simple-to-perform bone scans. But for all its inefficiencies, Medicare conducts periodic cost effectiveness analyses, and they have wizened up to the game. In 2007 they decided to cut bone scan reimbursement from $140 to $60, based on expectations that the scanners should get cheaper with scale, and the procedure was much less laborious to doctors than previously assumed.
Of course those groups and the bone-related medical community were outraged, and the decision may get overturned. They want every woman over 65 to get scanned yearly, and maybe some men too. But mass screening is a double-edged sword. They help identify truly needy patients, but also flag many false-positives. That is why the NIH recently changed its mammogram guidelines for women, raising the recommended starting age from 40 to 50. This decision is controversial, but their complex data suggested that the scans don't improve public health enough to justify their costs (worrisome specks on a scan require the patient to get a biopsy, which ends up causing stress and revealing nothing).
Merck also won approval for a low-dose version of Fosamax targeted for potential OP patients. So even though their risk of a debilitating bone break was no different than their general demographic, they could be put on a daily regimen just because a bone scanner reported that they were in the vague OP risk zone. Even some athletic, pre-menopausal women were classified as osteopenic (though that is no guarantee they will be osteoporotic later in life). "Mild bone thinning" isn't so bad, like graying hair or wrinkles. It's part of aging. But "osteopenia" sounds scary, right? Gradually wasting away, and maybe losing your freedom and mobility from a sudden fall. No one wants to die like a zombie in a hospice facility. So take this magical pill every day and rest easy. And of course Merck blitzed the media with direct-to-consumer advertising, and word spread among seniors. From 1994-1999, the number of bone scans performed in the US increased from 77K to 1.5M (yet still only 13% of women over 65 get the scan, so Merck has more work to do), and orders for scanners went up 500%.
This is great news, right? There are several positive Fosamax papers published, but a recent study from the Univ. of Washington concluded that Fosamax was only effective in reducing the risk of spinal fractures (especially for patients who have already had a break), which is only a tiny subset of total fractures for the elderly. That makes sense, since your bones respond to a fracture by dumping a bunch of new, low-quality bone on the injury site (like a quick and dirty spot-weld), so Fosamax's mechanism of action should preserve that from deterioration. Though the injury site may never recover to original strength with impaired bone-eating cells. For the prevention of more common hip or leg breaks, the drug was no better than placebo. So even though it results in denser bones biologically, if that doesn't translate into better clinical outcomes, then what's the point? If grandma falls on her driveway, probably 2% more bone density won't save her. Unfortunately no studies are planned to examine the long-term effects of Fosamax, which bewilders me because I thought the FDA requires that. But researchers are concerned that the drug may actually increase fracture risk over time, since it impairs micro-damage healing. If you just dump a bunch of steel onto an already craggy bridge, you may be doing more harm than good (as we in the SF area know).
In closing, the Fosamax story mirrors many drugs out there in your parents' medicine cabinet. Fosamax sales doubled from 2001-2004, and are now over $3B/year. It is on the top-10 list of all-time blockbuster drugs. Although Merck's patent recently expired, brand-name Fosamax costs $90/month, which translates to $16.2K for a patient taking it from age 70 to 85 (excluding medical labor costs). Yes it's true that the drug does help a subset of patients who really need it, and has allowed some seniors to enjoy life longer. But the caveat with preventative drugs is we'll never know if the patient would have been relatively okay without them. The drug has also sickened and killed others. Eating right, weight-bearing exercise, and vitamins also promote bone strength (and don't have side-effects). And to be clear, Fosamax doesn't generate more bone for seniors, it just slows normal or pathological bone loss (so it can't "reverse" OP). But don't worry, the industry took notice and next-generation bone drugs are in development. The "business of medicine" is not so altruistic. Sometimes pharma will persuade doctors, device makers, and the government to tailor diagnoses (or even invent diseases) to fit their drug. And if demand isn't high, they will make it so with marketing campaigns, lobbying, and low-dose or "preventative" formulations for people who "could be at risk". Too bad nothing exists in the 2009 health reform bill to expose or regulate this.
http://www.npr.org/templates/story/story.php?storyId=121609815
http://en.wikipedia.org/wiki/Fosamax
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