Drugs for Osteoporosis
Several classes of drugs have been developed to treat osteoporosis. These vary
in their effectiveness in reducing the risk of fractures.
Bisphosphonates (see Box 1) have become the mainstay of osteoporosis treatment
because, among the available medications, they have the best risk-benefit profile. For example, older drugs for preventing
fractures, such as estrogens, increase the risk of breast cancer as well as heart disease, and their risks outweigh their
benefits. The bisphosphonates are also very heavily advertised.
Bone is constantly being absorbed and reconstructed, a process called “remodeling.”
Reconstruction predominates into our 20s, when bone quantity and quality peak. After that, the quantity and quality of our
bones begins to decrease and the risk of fractures may therefore increase. In women, the decline becomes more pronounced after
Bisphosphonates work by interfering with cells that absorb bone.
When to Use a Bisphosphonate
Before beginning any medication, it is important to know how much you stand to benefit
because you may be exposing yourself to dangerous side effects. (See the November 2008 issue of Worst Pills, Best Pills News for a review of ways of determining your risk of bone fractures.)
Bisphosphonates are intended to prevent fractures. But the benefit is not the
same for all people. A straightforward way to think about how a bisphosphonate might benefit you is in terms of primary
and secondary prevention of fractures — when used to prevent a first fracture from occurring, it is called primary
prevention; when used to prevent a subsequent fracture from occurring in someone who has already sustained a fragility
fracture, it is called secondary prevention.
Sometimes the existing data about a drug make it difficult to understand its
effects in straightforward terms. Reflecting this difficulty, a recent analysis of all major clinical trials of alendronate
using a slightly different (and technically confusing) definition of primary and secondary prevention, provides a relatively
straightforward assessment of its benefits:
Patients taking alendronate for primary prevention (first fracture)
had the same number of hip fractures as those taking a placebo; in other words, alendronate made no difference for the most
serious type of fracture. Over five years, only two fewer patients out of 100 suffered a vertebral fracture if they took alendronate.
Risedronate (ACTONEL) did not decrease the risk of any fractures for primary
prevention. Studies of primary prevention with ibandronate (BONIVA) and zolendronate (RECLAST) have yet to be performed.
Box 1. Bisphosphonates Approved for Prevention and/or
Treatment of Osteoporosis|
• Alendronate (FOSAMAX)
• Risedronate (ACTONEL)
• Zoledronic acid (RECLAST)
When used for secondary prevention of fractures (subsequent
fractures), the number of women who would need to be treated with alendronate for five years to prevent one hip fracture was
100. Six fewer patients per 100 sustained vertebral fractures if they took alendronate for five years; these findings are
similar for the other bisphosphonates.
These results are not especially impressive. Moreover, little is known about
the use of bisphosphonates for longer than five years. A 10-year study of alendronate concluded that patients receiving treatment
beyond five years maintained an increased BMD compared to those who stopped at five years; however the number of hip fractures
was not statistically different between the two groups. This means that although an indicator of osteoporosis (BMD) was improved,
the outcome (the number of hip fractures) for the patients using alendronate was not better than for those who stopped using
the drug after five years. Using risedronate for up to seven years maintained BMD, and vertebral fractures occurred at a rate
similar to the previous year; however, there was no comparison group of patients who stopped risedronate after five years
so there is no way to know if continuing is beneficial.
Box 2: Strategies to
- Strength and balance training decrease fall-induced injuries, such
- Additional strategies that may decrease falls include:
- Reducing medications that cause sedation
- Treating heart conditions that may cause fainting (slow heart rate,
orthostatic hypotension, etc)
- Home hazard reduction (removing loose rugs and clutter, adequate
lighting, keeping wires behind furniture, etc.)
- Treating poor vision (cataract surgery)
- Strategies to decrease the force of impact, such as hip protecting
pads, in patients that are prone to fall can decrease fractures.
Serious Side Effects Associated With Bisphosphonates
Bisphosphonates, like all medications, have potential hazards.
Severe ulcers in the esophagus is a well-documented hazard. In order to decrease
esophageal irritation and possible ulcers, bisphosphonates (alendronate, ibandronate and risedronate) must be taken with an
empty stomach and a full glass of water.
You should remain in an upright position for at least 30 minutes after swallowing
Osteonecrosis of the jaw (destruction of the jaw bone) is a very serious complication;
it has most often occurred in cancer patients receiving intravenous bisphosphonates (ibandronate and zoledronate), but there
are also many cases in people using drugs such as alendronate for treatment of osteoporosis. This side effect often occurs
in the context of dental surgery/extractions...
Atrial fibrillation, an irregular and rapid heart beat, is a newly recognized risk
being investigated by the Food and Drug Administration. Lastly, incapacitating bone, muscle and joint pain is another known
hazardous side effect of bisphosphonates. Additionally, there is growing concern that prolonged interference with bone remodeling
cells by long-term bisphosphonate use may actually lead to fractures. (See next month’s Worst Pills, Best Pills News for a more in-depth discussion of this topic.)
Non-Drug measures Can Decrease Fractures
Just as there are many factors that can lead to fractures, there are more options
than just drugs for preventing osteoporosis-related fractures.
Falls are antecedent to most fractures. One’s risk of falling is a combination
of intrinsic characteristics and extrinsic hazards, some of which can be modified. There are measures that decrease one’s
risk of falling and can decrease fall-related injuries, including fractures (see Box 2).
In addition, smoking cigarettes and excessive alcohol consumption both negatively
impact bone; quitting smoking and decreasing alcohol consumption can decrease fracture risk.
Bringing it together
Although osteoporosis is an important component of fracture risk, the single-minded
focus on drugs for this condition risks neglecting other fracture-reducing interventions. We can achieve better application
of limited health care resources with a more thoughtful approach to prevention, incorporating modifiable risks for falling
and lifestyle modifications with prudent use of medications, like bisphosphonates, when evidence demonstrates a clinically
important reduction in fractures.