Long-term efficacy, safety, and patient acceptability of ibandronate in the treatment of postmenopausal osteoporosis

Abstract

Several second-generation bisphosphonates (BPs) are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration. A literature search using “ibandronate”, “postmenopausal osteoporosis”, “fracture”, and “bone mineral density” (BMD) revealed 168 publications. The Phase III BONE study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative risk reduction (RRR) in clinical vertebral fracture after 3 years. Non-vertebral fracture (NVF) reduction was demonstrated in a subgroup (pretreatment T-score ≤ −3.0; RRR 69%) and a meta-analysis of high annual doses (150 mg oral monthly or intravenous equivalent of ibandronate; RRR 38%). Hip fracture reduction was not demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long term safety is comparable to placebo over 3 years apart from flu-like symptoms which are more common with oral monthly and intravenous treatments. No cases of atypical femoral fracture or osteonecrosis of the jaw have been reported in randomized controlled trial studies. Ibandronate inhibits FPPS more than alendronate but less than other BPs which could explain rate of action onset. Ibandronate has a higher affinity for hydroxyapatite compared with risedronate but less than other BPs which could affect skeletal distribution and rate of action offset. High doses (150 mg oral monthly or intravenous equivalent) were superior to low doses (oral 2.5 mg daily) according to 1 year BMD change. Data are limited by patient selection, statistical power, under-dosing, and absence of placebo groups in high dose studies. Ibandronate treatment offers different doses and modalities of administration which could translate into higher adherence rates, an important factor when the two main limitations of BP treatment are initiation and adherence rates. However, lack of consistency in NVF reduction and absence of hip fracture data limits more generalized use of this agent.

Alfacalcidol Increases the Therapeutic Efficacy of Ibandronate on Bone Mineral Density in Japanese Women with Primary Osteoporosis

“…The MOVER study (Nakamura et al 2013) revealed that IBN was comparable to daily oral RIS in terms of reducing the incidence of vertebral fracture in Japanese patients with OP. Oral IBN at 2.5 mg daily decreased the risk of vertebral fracture by approximately 50% over a 3-year treatment period in the phase III BONE study (Inderjeeth et al 2014). Moreover, no atypical fracture or osteonecrosis of the jaw occurred in these patients, likely due to the lower affinity of IBN for hydroxyapatite than other BPs apart from RIS (Inderjeeth et al 2014).…”

“…Oral IBN at 2.5 mg daily decreased the risk of vertebral fracture by approximately 50% over a 3-year treatment period in the phase III BONE study (Inderjeeth et al 2014). Moreover, no atypical fracture or osteonecrosis of the jaw occurred in these patients, likely due to the lower affinity of IBN for hydroxyapatite than other BPs apart from RIS (Inderjeeth et al 2014). Thus, IBN represents a good therapeutic option in terms of fewer adverse effects than other BPs.…”

“…Injectable IBN formulations that allow for quarterly intravenous 3 mg bolus injections for OP treatment have since become available in the US and other countries. When administered intravenously, the bioavailability of IBN increases to as high as 100% and patients no longer need to manage food intake before and after treatment (Inderjeeth et al 2014). In 2013 in Japan, a new IBN formulation enabling monthly intravenous 1 mg bolus injections was approved and marketed as Bonviva ® (Chugai Pharmaceutical Co. Ltd., Tokyo, Japan).…”

Value Changes in Bone Turnover Markers and Bone Mineral Density Using Ibandronate in Japanese Postmenopausal Osteoporotic Patients

“…However, Rakel et al have reported that patients should not lie down for 60 min before the first food or drink which could reduced patient compliance [3]. Alternatively, ibandronate (IBN) can be infused intravenously to enhance its bioavailability to as high as 100% [4].…”

“…In addition, no atypical fracture or osteonecrosis of the jaw was detected in this clinical trial. IBN has a lower affinity for hydroxyapatite than other BPs apart from RIS [4]. Therefore, it might be a better option for osteoporotic treatment from the viewpoint of fewer adverse effects.…”