What’s best for your patients?
All these bisphosphonates have demonstrated efficacy for the secondary prevention of vertebral fracture. All except ibandronate have demonstrated efficacy for nonvertebral fracture, as well, and the evidence suggests that ibandronate will also be effective if adequate doses are given. Thus, for women at significant risk for fracture, it seems clear that the benefits of treatment outweigh the risks. The case is not so clearcut for women at lower risk. Evidence to support the use of bisphosphonates for primary prevention is limited, other than for alendronate—which has been shown to provide primary prevention of vertebral fracture.
Which bisphosphonate is best depends on patient preferences and individual profiles. (See “How would you treat these patients?”.) In the absence of head-to-head RCTs, it isn’t possible to comment on the relative efficacy of the various bisphosphonates or their adverse event profiles. Indeed, the authors of the 2 Cochrane reviews completed to date note that trial participants have been healthier, with fewer comorbidities, than many of the postmenopausal women seen by primary care physicians. Head-to-head studies conducted in family practice settings would be an important addition to the body of evidence for the prevention of osteoporotic fracture.
How would you treat these patients?
CASE 1 Mrs. A is an active 67-year-old in good health. On a recent hike, she lost her footing and sustained a Colles’ fracture when she fell, although her fall was only from standing height. Now, you are concerned that she might have osteoporosis.
A dual-energy x-ray absorptiometry (DXA) scan confirms this suspicion: Mrs. A’s lumbar spine T-score is –2.6. A dietary review reveals that she has a satisfactory calcium intake, and lab work shows that her serum vitamin D levels are normal. Mrs. A wants to discuss treatment options with you.
What immediate treatment do you consider?
Mrs. A has no contraindications to any FDA-approved treatment for osteoporosis; you suggest she begin taking bisphosphonates, explaining that they are first-line treatment to prevent subsequent osteoporotic fractures. You briefly discuss other options, but note that raloxifene only reduces the risk of vertebral fractures and parathyroid hormone is effective (but very expensive) and requires daily injections, and is therefore generally used for severe osteoporosis. Your patient asks about bisphosphonates’ side effects, particularly the serious jaw problems she’s heard about.
You explain that for the most part, oral bisphosphonates are well tolerated, but that there is a potential for upper gastrointestinal (GI) problems—which is why it’s important to remain upright for at least 30 minutes after taking the medication. You tell her that the risk of developing osteonecrosis of the jaw is very low when the medication is taken at the doses needed for osteoporosis treatment, but that the risk may increase after tooth extraction or dental surgery. Mrs. A has no current dental symptoms and at her usual yearly dental check-up 9 months ago, there were no problems noted, so dental review before starting treatment is not needed. Should she develop any jaw pain, however, she should see you or her dentist immediately.
You also advise her of the possible link between bisphosphonates and atypical femoral fracture, but point out that such fractures are extremely rare—and that the medication prevents far more fractures than it has the potential to cause. You tell her to contact you immediately if she develops pain in the groin or thigh or experiences GI distress.
Which bisphosphonate do you prescribe?
You inform Mrs. A that alendronate has the longest follow-up data of the oral bisphosphonates and has demonstrated efficacy for the secondary prevention of wrist fractures, that risedronate and ibandronate have the advantage of being able to be taken monthly rather than weekly, and that zoledronic acid can be administered in a yearly infusion. She opts for alendronate. You prescribe a weekly dose of 70 mg and ask her to return in 3 months, and to call before then if any problems arise.
CASE 2 Mrs. Y, age 82, recently sustained a fractured femoral neck, which was treated surgically at the local hospital. She was discharged with a prescription for alendronate to treat her osteoporosis and prevent further fractures; her husband has brought her in today to get a new prescription.
During the visit, he reminds you that Mrs. Y has problems with memory. He also says he’s finding it increasingly difficult to ensure that his wife remains upright for 30 minutes after taking alendronate, and that she has begun complaining of indigestion.