Osteoporosis Prevention Guidelines

When is drug treatment for osteoporosis prevention indicated?

At age 50, about 50% of white women are osteopenic. Only a third of these osteopenic women will progress to osteoporosis if left untreated. The primary means used to prevent osteoporosis had been estrogen-containing regimens until 2002 when the Women’s Health Initiative date reported that estrogen plus progesterone caused breast cancer, heart attack, and stroke. By 2006, reports linking Fosamax to osteonecrosis of the jaw and atypical fractures of the femur began to emerge. There was also a growing realization that prolonged suppression of bone remodeling with potent bisphosphonates was not a healthy practice. Remodeling removed devitalized bone and repaired microfractures caused by normal strain. Retained dead bone in the skeleton that became brittle as the bone became naturally more crystallized.

Discussions between stakeholders in the medical and research community took place with interested parties at the US FDA. The questions centered on this question; why expose all osteopenic women to potentially harmful drug therapy to prevent osteoporosis when the majority of them will never develop it?

As a result, the agency made two decisions. The first was to not to provide a pharmaceutical with a general osteoporosis prevention indication as was done for several products previously including Fosamax, Actonel, and Reclast. Secondly, the agency issued a Dear Doctor letter with new guidance to clinicians on continuous use limitations for the drugs in the bisphosphonate class.

Important Limitations of Use from the Fosamax Label
The optimal duration of use has not been determined. The safety and effectiveness of Fosamax for the treatment of osteoporosis are based on clinical data of four years duration. All patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. Patients who discontinue therapy should have their risk for fracture re-evaluated periodically.

In the Dear Doctor letter, the agency recommended a “drug holiday” of a couple of years before resuming treatment “if needed it.” If the patient was high risk for fracture, then the practitioner should use their clinical judgment to decide whether to discontinue treatment of not.

The answer to should we prescribe drug therapy to prevent osteoporosis in women with DXA diagnosed osteopenia not at unusually high risk for osteoporosis was no. The agency decided to withhold exposing them to new drugs for osteoporosis prevention until they become osteoporotic. They did allow for situations where there was a compelling reason to think that the patient would become osteoporotic. Qualifying reasons including 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.