Postmenopausal osteoporosis: Another approach to management

Also discuss with patients the importance of adequate supplementation with calcium and vitamin D. All patients with osteoporosis should consume at least 1200 mg of calcium and 800 to 1000 IU of vitamin D each day.⁹

Oral bisphosphonate therapies are effective …
Oral bisphosphonates (alendronate, risedronate, and ibandronate) effectively reduce fracture risk at various skeletal sites, and are generally safe and well tolerated. In a 3-year clinical trial involving postmenopausal women with low femoral neck BMD and at least 1 baseline vertebral fracture, alendronate 10 mg/d, compared with placebo, reduced the risk of vertebral fracture by 47% (8% vs 15%; absolute risk reduction [ARR], 7%) and hip fracture by 51% (1.1% vs 2.2%; ARR, 1.1%).¹⁰ Risedronate 5 mg/d has been shown to reduce the risk of vertebral fracture compared with placebo by up to 49% (18% vs 29%; ARR, 11%)¹¹ and nonvertebral fracture by up to 39% (5.2% vs 8.4%; ARR, 3.2%)¹² in similar populations. Oral ibandronate reduced the risk of vertebral fracture by 52% (4.7% vs 9.6%; ARR, 4.9%) at doses of 2.5 mg/d compared with placebo; this study was not powered to assess hip fracture reduction, and there was a similar number of nonvertebral osteoporotic fractures in both groups.¹³

… but patients have trouble with compliance
Rates of compliance (taking medication regularly and properly) at 1 year are poor, ranging from 30% to 55%.^14-16 Studies show a strong link between poor compliance with oral bisphosphonates and increased fracture rates, as well as increased health care costs.^15-20

Compliance problems associated with oral bisphosphonates may be attributed, in part, to their complex dosing requirements.¹⁴ Because these agents are poorly absorbed, patients must fast overnight before ingestion, and then avoid eating, drinking, or taking other medications for 30 to 60 minutes afterward. To reduce the potential for gastrointestinal (GI) irritation, patients must also maintain an upright position for at least 30 to 60 minutes after ingestion. Even when health care providers give complete instructions, between 25% and 50% of patients disregard at least 1 requirement.^21,22

The complex dosing regimens with oral bisphosphonates may be particularly challenging for patients with cognitive deficits. Noncompliance also rises with an increase in the number of comorbid conditions, with an increase in the number of medications a patient takes unrelated to osteoporosis, and with older age.²³

Studies examining persistence (the length of time a patient continues treatment) with osteoporosis therapy have confirmed that 32% to 55% of patients stop taking their oral medications for osteoporosis within 1 year.^14,15,23,24 Several studies have reported that weekly dosing is associated with greater persistence than daily osteoporosis therapy.¹⁴ Monthly dosing may yield additional improvements. For example, an open-label, randomized trial found that patients who received once-monthly ibandronate and support measures showed greater persistence at 6 months, compared with those receiving weekly alendronate (56.6% vs 38.6%, P<.0001).²⁴ Nevertheless, weekly and monthly regimens result in only modest improvements in persistence, and approximately 50% of all patients discontinue therapy by 6 months.^14,24-26 The recent availability of IV bisphosphonates administered under medical supervision offers a potential advantage in increasing persistence.

What we know about the effectiveness of IV bisphosphonates

IV ibandronate 3 mg every 3 months and IV zoledronic acid 5 mg every 12 months are approved for the treatment of postmenopausal osteoporosis. Health care professionals can provide the ibandronate IV injection or zoledronic acid infusion in their office or refer patients to a local provider or infusion center.

Ibandronate. The effectiveness of IV ibandronate is based on clinical trials with daily oral ibandronate, such as the BONE (oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe) study (FIGURE 1).

The DIVA (Dosing IntraVenous Administration) study compared IV ibandronate 3 mg every 3 months (n=471) with daily oral dosing with ibandronate 2.5 mg (n=470) in women with postmenopausal osteoporosis.²⁷ The IV regimen was significantly superior to daily oral dosing, with increases in mean lumbar spine BMD of 4.8% for the IV formulation and 3.8% for daily oral therapy (P<.001). Similar improvements in BMD occurred at other bone sites.

Zoledronic acid. The effectiveness of IV zoledronic acid, administered over a period lasting at least 15 minutes, was shown in the 3-year Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT).²⁸ An annual infusion of zoledronic acid 5 mg in postmenopausal women with osteoporosis (n=3875) compared with placebo (n=3861) reduced the risk of hip fractures, vertebral fractures, and nonvertebral fractures by 41% (1.4% vs 2.5%; ARR, 1.1%), 70% (3.3% vs 10.9%; ARR, 7.6%), and 25% (8% vs 10.7%; ARR, 2.7%), respectively (P≤.002) (FIGURE 2). The numbers of patients needed to treat (NNT) to prevent 1 fracture at 3 years were 91, 13, and 37 for hip, vertebral, and nonvertebral fractures, respectively. IV zoledronic acid also significantly increased BMD and reduced bone turnover markers.