A reader recently complained that her elderly mother had faithfully taken the medication prescribed to protect her osteoporotic bones from fracture but still broke her hip as she walked from her bedroom to the bathroom one morning. The older woman recalled that she had felt her hip give way and then fell, not the other way around.
This is not an uncommon report of low-trauma fractures occurring despite treatment with drugs licensed to prevent them. The surprise among people who have these fractures, and among their family members, may reflect a failure of prescribing doctors to explain the drugs’ limitations adequately — or wishful thinking on the part of patients who believe too strongly in the magic of modern medicine.
Here are the facts: Osteoporosis is a disease that develops over the course of many decades, and the drugs thus far licensed to limit its consequences are far from perfect. Although all have been shown to reduce the risk of osteoporotic fractures, none come even close to preventing them entirely.
And all have side effects that can limit their usefulness in many people whose bones have become overly porous and fragile.
These facts should not stop people who can benefit from using such medication. But before deciding whether to do so, and which drug to try, it pays to review what is known of their relative benefits and risks, and what else may help as well.
It is also important to realize that while the drugs can increase bone mass as shown on bone mineral density tests, the evidence is limited for their ability to prevent fractures in people whose bones have lost mass but have not yet become osteoporotic, unless they have already suffered a low-trauma fracture. Osteoporosis is defined as having a bone mineral density T score — the standard measure of bone density — of minus 2.5 or lower. Lesser degrees of bone loss, known as osteopenia, may or may not benefit from drug therapy.
Drugs on the Market
There are basically two types of medications on the market. Most prominent are those called antiresorptives, drugs that reduce bone breakdown by limiting the release of calcium from bone into the blood. A newer type is called anabolic because it promotes new bone formation.
The first drug licensed to counter osteoporosis, Fosamax, is now available generically as alendronate, which can be taken once a day or, at a higher dose, once a week. Likewise with a sister drug, Actonel (risedronate). A reluctance on the part of many patients to adhere to a daily or weekly regimen led to the development of Boniva (ibandronate), administered by an intravenous injection every three months. To further simplify the frequency of administration, Reclast (zoledronic acid) was developed as a once-a-year intravenous treatment.
All of the above are in a class of drugs called bisphosphonates, which can increase bone mass in men and women by reducing bone turnover. The oral treatments require that patients take them first thing in the morning on an empty stomach with plain water. They must also refrain from eating or drinking anything and remain sitting or standing for 30 to 60 minutes afterward.
Actonel, alendronate and Boniva have been shown in three-year studies of postmenopausal women to reduce vertebral fractures by 41 percent to 50 percent, and less for other kinds of fractures.
A three-year study of Reclast found it to be somewhat more effective, with a 70 percent reduction in vertebral fractures, 41 percent in hip fractures and 25 percent in other fractures in postmenopausal women with osteoporosis.
Gastrointestinal problems are the main side effect associated with oral bisphosphonates: difficulty swallowing, inflammation of the esophagus and stomach ulcer, which can sometimes occur even when patients rigidly follow instructions. In rare cases, especially among people with cancer who take the drugs for more than five years, the bisphosphonates can cause a breakdown of the jaw. Visual disturbances have also been reported.
In a large study of Reclast, there was also a worrisome increase in atrial fibrillation — an irregular heart rhythm — not known to occur with other bisphosphonates.
Side Effect of Concern
But perhaps the most disturbing side effect of these drugs has been a growing number of patients who experience an otherwise uncommon injury — a low-trauma fracture of the thigh bone or other major bone — and a delay in healing or complete failure of a fracture to heal, especially after many years on bisphosphonates. It is believed that in slowing bone turnover, the drugs may impede the repair of normally occurring microfractures and eventually result in a major fracture.
These side effects have prompted a warning that after five years on bisphosphonates, people should take a break from the drugs for at least a year.
Another effective antiresorptive drug is Evista (raloxifene), which has an added advantage of reducing the risk of breast cancer, but the disadvantage of increasing the risk of deep vein blood clots and hot flashes. Estrogen, too, is an effective antiresorptive that can cause clots, but unlike Evista, it is not recommended for women with a history of breast cancer.
Somewhat less effective at reducing vertebral fractures is calcitonin, a naturally occurring hormone sold as Fortical and Miacalcin. It can be prescribed for men and for women who are at least five years past menopause. Calcitonin can be taken orally, as a daily nasal spray or by injection into muscle or fatty tissue.
Finally, there is the bone-building drug Forteo (teriparatide), which must be self-injected once a day. This human parathyroid hormone can reduce vertebral fractures by 65 percent and other fractures by 53 percent within 18 months in patients with osteoporosis. Leg cramps and dizziness are occasional side effects. Its use is currently limited to two years, and it is sometimes combined with a bisphosphonate to enhance bone protection.
Still under study is an entirely new bone drug, denosumab, a human monoclonal antibody. The drug inhibits a receptor that activates cells called osteoclasts that break down bone. In a large three-year study, denosumab, given by injection every six months to postmenopausal women with osteoporosis, reduced vertebral fractures by 68 percent and hip fractures by 40 percent.
No increase in side effects was noted in this study, but because the receptor also occurs on immune cells, patients will be monitored for years to see if any increase in cancer or infections occurs. In another small study, denosumab also helped protect the vertebrae of elderly men being treated for prostate cancer.