What is the optimal duration of bisphosphonate therapy?
ABSTRACTIt is reasonable to stop bisphosphonates after 5 years of use and then to follow patients with markers of bone turnover. As long as the levels of these markers remain reduced, adding an antiresorptive drug does not make physiologic sense.
KEY POINTS
- Bisphosphonates reduce the risk of osteoporotic fractures, including devastating hip and spine fractures.
- As with any drugs, bisphosphonates should not be used indiscriminately. They are indicated for patients at high risk of fracture, especially those with vertebral fractures or a hip bone density T score lower than −2.5.
- There is little evidence to guide physicians about the duration of bisphosphonate therapy beyond 5 years. One study with marginal power did not show any difference in fracture rates between those who continued taking alendronate and those who discontinued after 5 years (JAMA 2006; 296:2927–2938).
- Evidence is accumulating that the risk of atypical fracture of the femur increases after 5 years of bisphosphonate use.
- Anabolic drugs are needed; the only one currently available is teriparatide (Forteo), which can be used when fractures occur despite (or perhaps because of) bisphosphonate use.
Bone density is less helpful, but reassuring
Bone density is less helpful because it decreases even though the markers of bone resorption remain low. Although one could argue that bone density is not helpful in monitoring patients on therapy, I think it is reassuring to know the patient is not excessively losing bone.
Checking at 2-year intervals is reasonable. If the bone density shows a consistent decrease greater than 6% (which is greater than the difference we can see from patients walking around the room), then we would re-evaluate the patient and consider adding another medication.
If the bone density decreases but the biomarkers are low, then clinical judgment must be used. The bone density result may be erroneous due to different positioning or different regions of interest.
If turnover markers are not reduced
If a patient has been prescribed a bisphosphonate for 5 years but the NTx level is not reduced, I reevaluate the patient. Some are not taking the medication or are not taking it properly. The absorption of oral bisphosphonates is quite low in terms of bioavailability, and this decreases to nearly zero if the medication is taken with food. Some patients may have another disease, such as hyperparathyroidism, malignancy, hyperthyroidism, weight loss, malabsorption, celiac sprue, or vitamin D deficiency.
If repeated biochemical tests show high bone resorption and if the bone density response is suboptimal without a secondary cause, I often switch to an intravenous form of bisphosphonate because some patients do not seem to absorb the oral doses.
If a patient has had a fracture
If a patient has had a fracture despite several years of bisphosphonate therapy, I first check for any other medical problems. The bone markers are, unfortunately, not very helpful because they increase after a fracture and stay elevated for at least 4 months.54 If there are no contraindications, treatment with teriparatide (Forteo) is a reasonable choice. There is evidence from human biopsy studies that teriparatide can reduce the number of microcracks that were related to bisphosphonate treatment,13 and can increase the bone formation rate even when there has been prior bisphosphonate treatment.55–57 Although the anabolic response is blunted, it is still there.58
If the patient remains at high risk
A frail patient with a high risk of fracture presents a challenge, especially one who needs treatment with glucocorticoids or who still has a hip T score below −3. Many physicians are uneasy about discontinuing all osteoporosis-specific drugs, even after 5 years of successful bisphosphonate treatment. In these patients anabolic medications make the most sense. Currently, teriparatide is the only one available, but others are being developed. Bone becomes resistant to the anabolic effects of teriparatide after about 18 months, so this drug cannot be used indefinitely. What we really need are longer-lasting anabolic medicines!
If the patient has thigh pain
Finally, in patients with thigh pain, radiography of the femur should be done to check for a stress fracture. Magnetic resonance imaging or computed tomography may be needed to diagnose a hairline fracture.
If there are already radiographic changes that precede the atypical fractures, then bisphosphonates should be discontinued. In a follow-up observational study of 16 patients who already had one fracture, all four whose contralateral side showed a fracture line (the “dreaded black line”) eventually completed the fracture.59
Another study found that five of six incomplete fractures went on to a complete fracture if not surgically stabilized with rods.60 This is an indication for prophylactic rodding of the femur.
Teriparatide use and rodding of a femur with thickening but not a fracture line must be decided on an individual basis and should be considered more strongly in those with pain in the thigh.
