Medications for Osteoporosis
All right, you knew that it would have been better to go out for tennis when you were in seventh grade and train for track in high school, mind your minerals in your teens, and exercise big time after college. You’re not a heavy drinker and you quit smoking, but now you have osteoporosis. What to do? Is it too late?
The dietary considerations outlined in chapter 3 apply to people who have osteopenia or osteoporosis as well as those who just want to avoid it. Vitamin D is for everyone. Lifestyle choices play a hefty part too. But let’s turn to medications, which are reserved for the people that actually have low or rapidly falling bone mineral density. The medicines presented here are only for the 200-million-plus people who have that problem. Since you’ll have to consult a physician, and his or her judgment is the one you listen to (or you must get another doctor), we focus on the medicines themselves, not when and whether you should take them.
Fosamax (Alendronate)
Fosamax was the first modern drug to treat osteoporosis that really took hold of the American medical community. At this writing in 2009 it is still the most frequently prescribed, though it was introduced many years ago and a number of other medications have been developed since. It is a bisphosphonate, a class of drugs that inhibit the osteoclasts, the cells that reabsorb calcium from bones. In osteopenia and osteoporosis, osteoclasts destroy bone faster than osteocytes lay it down. Fosamax slows down the destruction. That can tip the balance, and in a study of 3,658 women, Fosamax reduced the incidence of hip, vertebral, and wrist fractures by 53 percent, 45 percent, and 31 percent respectively.1
A randomized placebo-controlled Canadian study shows that alendronate is as effective in men as it is in women, regardless of the men’s male (or female) hormone levels, or the magnitude of the patients’ bone resorption. In either gender, patients’ BMDs usually gain 6 percent in the first year of use and 2 percent each year thereafter. Ninety-five percent of the patients who have participated in clinical trials of this drug show a significant increase in BMD. The risk of any kind of fracture goes down about 50 percent. The usual dose is 5 mg daily for osteopenia, 10 mg per day for osteoporosis.2
The most common side effects are gastrointestinal. Patients are advised to stay clear of food for at least an hour after taking the medication. Acid reflux, nausea, and irregular bowels, along with muscular, abdominal, and bone pain, are the main things to worry about, and they are not uncommon. Other side effects, such as osteonecrosis (disintegration of the jawbone, auditory canal, or other bones) and slower healing of fractures that do occur have been discussed in the media over the past few years, but are estimated to be quite unusual, related to dental surgery, cancerous conditions, and the duration of treatment. In addition, there is evidence that bisphosphonates stay in the body for long periods of time, possibly throughout life, and can cross the placenta.3
This does not sound so bad. Few osteoporotic patients are of childbearing age, and don’t you want the good effects to stay around and help you for a long time? Unfortunately the adverse effects are strong enough, or patients’ resolve is weak enough, that compliance is a major issue. One recent study found that less than 35 percent of the people given prescriptions for this medication actually stay on it long enough to make it “therapeutically relevant.”4
Actonel (Risedronate)
A second bisphosphonate, Actonel, has many of the same negative side effects as Fosamax, but it is a coated capsule. This lowers the chance of esophageal irritation.
Boniva (Ibandronate)
More recently, and possibly because of the low compliance seen with the other bisphosphonates, Boniva, a once-a-month oral or injectible drug, has been introduced.
Ibandronate works the same way the other two bisphosphonates do, slowing down the resorption of bone by osteoclasts, but is so powerful that patients are strongly advised not to take it unless they are also taking calcium and vitamin D to supply the building blocks for healthy bone, have no kidney problems that would disturb their bodies’ relatively constant levels of serum calcium, and can remain vertical for at least an hour after taking the medicine to minimize gastrointestinal side effects. Major adverse effects include abdominal pain, hypertension, joint pain, nausea, upset stomach, and diarrhea.
Reclast (Zoledronic Acid)
Recently things have gotten even simpler. Reclast, perhaps the ultimate bisphosphonate, is given as an annual intravenous infusion. Only 5 mg have proven 50 percent more effective than Actonel in treating people with osteoporosis acquired through exposure to steroids, and over four times more effective in building bone mass as a preventive measure.5 Atrial fibrillation is a major adverse effect.
Regardless of which bisphosphonate one chooses, it is always wise to use calcium and vitamin D supplements as well. These nutritional supplements are used by controls and intervention patients in most of the studies that support the efficacy of these medications.6
Denosumab
As of 2009, denosumab is not yet on the market. Denosumab is an antibody that prevents the activator molecule RANKL from stimulating cells to evolve into osteoclasts, therefore reducing bone resorption. Side effects reported were few, and the gastric upset that is commonly associated with oral bisphosphonate use was substantially reduced. Increase in bone mass was greater with denosumab than with alendronate in a study of 412 patients, and bone synthesis was in full swing after only three days. Early trials have begun to find separate cortical and trabecular effects, and also indicate that the drug slows the development of rheumatoid arthritis.7 A recent radiological study using densitometry and examination of bone structure suggests that denosumab actually improves bone quality.8
Estrogen, Progesterone, and Selective Estrogen Receptor Modulators (SERMs)
Hormone replacement therapy after menopause (HRT), seemed to be in the headlines almost every day for a while. Women commonly used it to tame the changes that come with menopause. Many conflicting studies associate HRT with an increased risk of uterine and breast cancer, heart disease, and thrombosis, but also with an improvement in bone mineral density. Birth control medications, premenopausal (and pharmaceutically quite different) forms of HRT, keep their users’ bones quite youthful much of the time. A popular compromise solution is for menopausal women to take half the usual HRT dose, either orally or transcutaneously through a skin patch. The patch, enables the body to acquire the estrogen and/or progesterone without the hormones passing through the liver. Progesterone alone increased the bone mineral density of first-year users up to 10 percent with approximately 4 percent improvements each year thereafter.
Progesterone medications are frequently combined with estrogens such as estriol, estradiol, and estrone. Of these, 17 alpha-estriol appears to be the least toxic, actually reducing the progress of breast cancer, and the one of all of the estrogens that has a very low likelihood of re-initiating monthly menstruation.
Evista (Raloxifene)
This is an interesting medication that some, but not all, of the body’s cells see and treat just as they do estrogen. Bone cells respond as they would to estrogen, reducing reabsorption of calcium, but other tissues are actually blocked by this drug from responding to any estrogen that the body happens to have around. It does not have estrogen’s effect on the heart, and actually decreases the risk of breast cancer. The same risk of blood clots associated with estrogen use does seem to come with Evista.
Similar medications, such as lasofoxifene, bazedoxifene, and arzoxifene, were in clinical trials in 2009. Bazedoxifene was approved by the FDA in 2007 and will probably be available by early 2010 under the tradename Viviant; it may be combined with conjugated estrogens. Aprela, the combination medication, is currently in mid-trial (a Phase III study). Lasofoxifene has been approved in Europe by the CHMP and has received committee approval from the FDA. Eli Lilly has stopped work on arzoxifene.
Miacalcin (Calcitonin)
Contrary to the once-popular song, the hip bone is connected to the bloodstream. We have already reviewed the perils of too-low concentration of calcium in the bloodstream which include massive muscle spasm and may affect the smooth muscle of the heart. The body is therefore totally justified in ruthlessly appropriating calcium from the bones, where more than 90 percent of the body’s calcium resides, in order to keep the whole organism running and intact. Calcitonin, a hormone synthesized in the thyroid gland, regulates and reduces the body’s tendency to reabsorb the bones’ calcium.
Just as estrogen and progesterone levels dwindle later in life, calcitonin levels fall as well. Salmon calcitonin is frequently used to supplement our natural supply, since it is much more potent than our own. Fish, of course, even the valiant salmon, have a different relationship with gravity, and have bones that are mainly muscle-strain-bearing, rather than weight-bearing. This may account for the fabulous power of the salmon calcitonin. More than 60 percent of the users of Miacalcin can expect improvement, often up to a 4 percent increase of bone mineral density, and 40 percent reduction in risk of fracture. It may be taken as a nasal spray, wherein lies its main but uncommon side effect, nasal irritation.
Being a biological product, Miacalcin is probably the drug of choice if gastric or other side effects prohibit the bisphosphonates, and cancer or other risks forbid hormone replacement therapy.
Forteo (Teriparatide)
Synthetic parathyroid hormone, teriparatide appears to increase bone mineral density and reduce vertebral and nonvertebral fractures without a substantial risk of raising calcium in the bloodstream to dangerous levels. It does this by tipping the balance in favor of bone build-up and slightly against bone breakdown. Both lower and higher doses of parathyroid hormone appear to favor build-up, but high doses (40 mg) were actually found to promote resorption at the forearm.9 A Harvard study of 1,637 patients found that once-a-day injections of 40 mg were only slightly more effective than 20 mg, but had a greater likelihood of causing nausea and headache, the other chief side effects.10
Besides vitamin D, parathyroid hormone is the only other known naturally occurring substance that in and of itself will build bone.11
Horse before Cart
Dr. George Kessler points out that three quarters of the people taking medicines for osteoporosis do not take calcium and vitamin D daily.12 He likens this to a contractor who has the electrician, the plumber, the roofers, the carpenters, and all the workmen assembled at a job site, but then does not deliver the electrical wires, the pipes, the shingles, or the lumber.
There are undeniable and also unpredictable side effects to all these medications. Although they are effective for prevention as well as remediation of low bone mineral density, those people with less than 2.5 standard deviation loss of bone might be wise to avoid them, in favor of a regimen that includes vitamin D, calcium, and exercise for a year or two, and then repeat a DEXA scan before embarking on any of the more rigorous and risky medical treatments. If there is substantial improvement, medication may not be necessary.