Osteoporosis: A quick update

Duration of treatment should be individualized based on specific patient factors, the pharmacologic agent, and, of course, adverse effects. However, no pharmacologic agent should be used indefinitely.⁶ In its clinical practice guidelines, the ACP recommends that patients be treated for 5 years with an appropriate pharmacologic therapy.⁸ The American Society for Bone and Mineral Research (ASBMR) Task Force recommends a review of therapy after 3 years with an intravenous bisphosphonate (BP; strength of recommendation [SOR]=C).¹⁷

Individualize duration of therapy based on patient factors and the pharmacologic agent being used, but no agent should be used indefinitely.

A review of 2 recent long-term trials analyzing the effects of BPs offers some additional guidance regarding duration of therapy in Caucasian postmenopausal women.¹⁸ In one study, women who received 10 years of therapy with alendronate reported fewer vertebral fractures than those who were switched to placebo after 5 years of treatment.¹⁹

In the second trial, which studied zoledronic acid, there were fewer morphometric vertebral fractures for those participants given annual injections for 6 years vs 3 years.²⁰ This trial found a significant transient increase in serum creatinine >0.5 mg/dL in the zoledronic acid treatment group.

These findings have prompted some experts in the field of osteoporosis to call for physicians to consider longer therapy with a BP (10 years with oral therapy or 6 years with intravenous therapy) in high-risk postmenopausal women (older women, those with a low hip T-score or high fracture risk score, those with a previous major osteoporotic fracture, and those who experienced fracture while on therapy) (SOR=B).¹⁸

Two rare adverse effects to keep in mind

The incidence of atypical femoral fracture, although rare (2-100 per 100,000 women), increases with duration of BP use. As a result, a drug holiday of 2 to 3 years should be considered for women with a low risk for fracture after 3 to 5 years of BP therapy (SOR=C).¹⁸

Osteonecrosis of the jaw (ONJ), also known as antiresorptive-associated osteonecrosis of the jaw, is a rare adverse effect of BPs that is associated with higher drug potency, higher cumulative dose, and parenteral route of administration, as well as other risk factors.^17,21 The American Association of Maxillofacial Surgeons (AAOMS) states that the risk of developing ONJ increases with use of oral BPs for more than 4 years;²² however, the Task Force of the ASBMR states that the evidence to support this is of poor quality.¹⁸ No recommendations on duration of therapy based on risk for ONJ have been made; however, AAOMS recommends discontinuation of oral BPs for a period of 2 months prior to, and 3 months following (or until osseous healing has occurred), elective invasive dental surgery for patients who have been taking an oral BP ≥4 years (SOR=C).²²

Review therapy after 5 years with an oral bisphosphonate and after 3 years with an intravenous one.

If a long-term drug holiday is selected, patients should be reassessed in 2 years. Shorter duration of follow-up is warranted for patients taking denosumab, teriparatide, or raloxifene, since bone loss will resume once therapy is discontinued.¹⁸

Because the benefits of BPs (in terms of reducing the risk of vertebral fracture) are significantly greater than the risks of an atypical fracture or ONJ, therapy should be started in appropriate patients, but duration of therapy should be monitored closely.

CORRESPONDENCE
Lovedhi Aggarwal, MD, 95-390 Kuahelani Avenue, Mililani, HI 96789; aggarwal@hawaii.edu.