Ibandronate treatment for osteoporosis: Rationale, preclinical and clinical development of extended dosing regimens

Abstract

Ibandronate is a potent nitrogen-containing bisphosphonate available as a once-monthly oral formulation for the treatment and prevention of osteoporosis. Preclinical experiments with estrogen-depleted rats, dogs, and monkeys demonstrated the efficacy of daily and intermittent ibandronate dosing. Initial clinical trials explored the optimal dosing regimens for oral administration in humans. The Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe (BONE) and Monthly Oral Ibandronate in Ladies (MOBILE) trials demonstrated that long-term daily and intermittent administration of ibandronate was efficacious for increasing bone mineral density, reducing markers of bone turnover, and preventing fractures, while maintaining bone quality. These preclinical and clinical ibandronate trials provided progressive evidence that a simple, long interval dosing regimen could offer efficacy and safety comparable with currently available bisphosphonates. It is anticipated that once-monthly ibandronate may have a positive impact on patient adherence, and ultimately, on fracture protection in osteoporotic women.

Biodistribution and Pharmacokinetic Studies of Bone-Targeting N-(2-Hydroxypropyl)methacrylamide Copolymer−Alendronate Conjugates

“…About half of alendronate dose may deposit to bone. The development of once per month oral dose (ibandronate) or once a year infusion (zolendronic acid) is patient friendly. However, bisphosphonates have some limiting side effects that include diarrhea, nausea, constipation, mild intestinal upset, severely suppressed bone turnover and possibility of development of osteomalacia and progressive osteolytic lesions resulting in lower patient compliance .…”

Diagnosis and therapy of osteoporosis in geriatric trauma patients: an update

“…Studies show that intravenous therapy with bisphosphonates is not inferior to the therapy with oral bisphosphonates concerning fracture risk. The compliance of the patients might be even higher in monthly intravenous applications than in taking it orally [25], [26].…”

An Atlas of Osteoporosis

“…A fast rate of bone loss and a low bone mineral density may contribute equally to future risk of fracture 58 . Fat postmenopausal women have higher endogenous estrogen production 61,62 , and it appears that fast bone losers have lower serum concentrations of estrogens than slow bone losers [63][64][65] . Some reports suggest that this difference is not related to initial bone mineral content, parity, or smoking habits, but to estrogen levels and fat mass 60 .…”

“…Preclinical experiments with estrogen-depleted rats, dogs, and monkeys demonstrated the efficacy of daily and intermittent ibandronate dosing 63,64 . Preclinical experiments with estrogen-depleted rats, dogs, and monkeys demonstrated the efficacy of daily and intermittent ibandronate dosing 63,64 .…”