Both originator and generic bisphosphonates are seen as first-choice treatments for osteoporosis and related ailments, but does the available literature support this view?

Patients at risk of bone fractures are commonly treated with bisphosphonate

Globally, only a fraction of orthopaedic patients who deserve to be on treatment are being treated. Only 20% of patients who present with an index fracture currently receive basic therapy or are offered screening for future fracture risk.

International guidelines recommend bisphosphonates as first-line therapy in men and postmenopausal women with osteoporosis, as well as glucocorticoid-induced osteoporosis. The efficacy of bisphosphonates for osteoporotic fracture has been consistently reported in randomised controlled trials enrolling large numbers of patients.

EFFICACY OF BISPHOSPHENATES

Studies show that bisphosphonates reduce the relative risk of vertebral fractures by between 40-50% and that of nonvertebral fractures by about 25-35% over a period of three years.

The Ibandronate Oral Advisory Consensus Document, endorsed by local expert Dr Stanley Lipshitch, reviewed the efficacy of Boniva 150mg (ibandronate) oral once-monthly for the treatment of osteoporosis in postmenopausal women. The document was drafted by key opinion leaders Drs Tobie de Villiers, Mike Davey, Bilkish Cassim and Willem de Lange.

The Effects of Oral Ibandronate Administered Daily or Intermittently on Fracture Risk in Postmenopausal Osteoporosis, also known as the BONE study, found that oral daily ibandronate demonstrated a 62% relative risk reduction in new vertebral fractures versus placebo. The Risk of Fracture in Women Treated with Monthly Oral Ibandronate or Weekly Bisphosphonates: The Evaluation of Ibandronate Efficacy (VIBE) database fracture study, found that monthly ibandronate 150mg orally demonstrated a significantly lower rate of vertebral fractures versus weekly oral bisphosphonates. They also found that 150mg was better.

The MOBILE study, a randomised, phase III, noninferiority study, found substantial increases in lumbar spine bone mineral density (BMD) in all treatment arms: 5%, 5.3%, 5.6%, and 6.6% in the daily and once- monthly groups (50mg + 50mg, 100mg, and 150mg), respectively, confirming that all once-monthly regimens were at least as effective as daily treatment.

HIP FRACTURE RISK REDUCTION EFFICACY OF IBANDRONATE

Substantial increases in proximal femur (total hip, femoral neck, trochanter) BMD were seen with 150mg producing the most pronounced effect. Independent of the regimen, most participants (70.5-93.5%) achieved increases above baseline in lumbar spine or total hip BMD, or both. Pronounced decreases in the biochemical marker of bone resorption, sCTX, observed in all arms after three months, were maintained throughout.

The long-term efficacy and safety of once-monthly ibandronate was studied in the extension to the two-year MOBILE study, the MOBILE-LTE. Patients from the MOBILE monthly ibandronate arms and 698 patients from all arms were reallocated to ibandronate 100mg monthly or 150mg monthly for a further three years.

The MOBILE-LTE study concluded that 150mg once-monthly oral ibandronate is an effective and well tolerated treatment for postmenopausal osteoporosis. The BMD at the proximal femur is maintained, with further small gains in lumbar spine BMD. The efficacy of once-monthly ibandronate is sustained over five years and there were no new safety signals.

Conclusion

The efficacy and safety of ibandronate has been demonstrated over five years. Originator bisphosphonate has demonstrated superior efficacy, safety and persistence compared to a generic bisphosphonate. Observational data over 12 months suggest that ibandronate fracture risk was not significantly different between patients receiving monthly ibandronate or weekly bisphosphonates for hip, non-vertebral or any clinical fracture.