In 2002, we learned that use of estrogen and progesterone for prevention of osteoporosis in the form or PremPro that was the drug used in the landmark Women’s Health Initiative study had significant serious side effects.
In the mid 2005, information surfaced about two new side effects associated with Fosamax treatment, one serious Atypical Fracture of the Femur and one bothersome in osteoporosis patients Osteonecrosis of the Jaw. There was also a growing realization that prolonged suppression of bone remodeling was not a healthy practice because it caused retention of old dead bone in the skeleton that became brittle as the bone crystals became more crystalline.
While half of white women over age 50, are osteopenic only a third of that osteopenic group becomes osteoporotic. By 2008, the US FDA and others were asking why expose all osteopenic women to potentially harmful drug therapy to prevent osteoporosis when the majority of them will never develop it?
The answer they came to was not to expose osteopenic women until they become osteoporotic unless there is a compelling reason to think that they will. Qualifying reasons to treat osteopenic, women and men with drugs to prevent osteoporosis have now been developed. They all involve being on a long-term drug therapy known to cause osteoporosis. Three come to mind:
- Aromatase inhibitors used as adjuvant therapy for breast cancer.
- Androgen deprivation therapy prescribed to men with prostate cancer.
- Glucocorticoids prescribed for a variety of medical conditions where the daily dose is equal to or greater than 7.5 mg of prednisone or its equivalent and the course of treatment is expected to last for more than 3 months.
There will probably be other indications added to this list.
It is of note from the forgoing discussing that as of 2009, the US FDA changed its policy and is no longer approving drugs for routine prevention of osteoporosis. To date, they have not rescinded the indications already granted to a number of agents including Reclast, Fosamax, Evista, and Actonel. I am unaware of any commentary indicating that they will remove this indication from these drugs.
I support this policy as applied to young postmenopausal women and men with DXA based osteopenia and no history of a fragility fracture typical of osteoporosis. Studies now show that the majority of these people will not develop osteoporosis during their lifetime. They are at low current and future risk for hip or major osteoporotic fracture when evaluated by any authoritative measure, like the WHO’s FRAX tool.
On the other hand, in my experience, there are many older people who are very like their younger peers that are at high risk for hip fracture in particular as predicted by the FRAX. High risk for hip fracture by FRAX means the risk for hip fracture over the next decade exceeds 3%. The National Osteoporosis Foundation has established the 3% threshold as the intervention point when drug therapy to lower hip fracture risk is warranted even in the absence of a T-score of <-2.5 or a fragility fracture.
I fully support this point of view too. Our principal focus is preventing the first osteoporotic fracture. Of all the fractures due to osteoporosis hip fracture is the most devastating to the person and most costly to our society. The FRAX is a validated instrument that accurately predicts who is at highest risk for hip fracture and guidance from the Scientific Advisory Board of the NOF provides expert opinion regarding at what point the level of risk becomes unacceptable. I use the FRAX and the NOF guidance for when to treat my patients. I explain to them that while they don’t have osteoporosis by DXA of fracture criteria their hip fracture risk has risen to above a threshold level where it is high enough to qualify as a surrogate for osteoporosis. Increasing age is often the driving force behind a rising FRAX. My patients understand and accept this explanation and readily agree to participate in the effort to maintain their skeletal health.