Original articleIntravenous intermittent neridronate in the treatment of postmenopausal osteoporosis
Introduction
Oral bisphosphonates have been used with success in the treatment of osteoporosis and two of these compounds, alendronate and risedronate, have been approved worldwide for the treatment and prevention of osteoporosis [1], [2], [3]. However, all bisphosphonates are poorly absorbed from gastrointestinal tract (<1%) and the absorption is lowered apparently to zero by the presence of any food in the stomach [4]. Therefore, oral biophosphonates should be taken in fasting conditions at least 30 min before any breakfast (including coffee). Oral amino-bisphosphonates are known to cause occasionally severe gastrointestinal side effects [5] and this can be at least in part prevented by taking the tablets with a large amount of water and by maintaining the upright position for half an hour. This dosing schedule is very inconvenient and it may be responsible of lack of compliance and thereby to poorer therapeutic outcomes. In addition, oral aminobisphosphonates are totally inaccessible to patients even transiently compelled to bed. These limitations have led to initial development of intermittent intravenous (IV) infusions of bisphosphonates. Such use appears to be justified by the pharmacodynamic characteristics of the compounds [4] and by the positive results obtained in a number of pilot or phase 2 clinical trials, particularly with ibandronate and zoledronate [6], [7]. Neridronate is an aminobisphosphonate structurally similar to alendronate and pamidronate: the compounds differ only in the number of methyl groups of the side chain—5 for neridronate, 3 for alendronate, and 2 for pamidronate [4]. It has been investigated for the treatment of Paget’s disease of bone [2], [8], [9], [10] and recently registered in Italy for the treatment of osteogenesis imperfecta [11]. Here, we report the results of a pilot controlled trial on the effect of this new aminobisphosphonate given bimonthly (IV) in the treatment of postmenopausal osteoporosis.
Section snippets
Patients and treatments
The study included 78 postmenopausal women from two distinct osteoporosis centers of Verona (Table 1). Women eligible for study participation had been postmenopausal for at least 5 years, were not older than 80 years, and had spine bone mineral density (BMD) at least −2.5 SD below peak. Excluded from participation were women with metabolic bone disease other than postmenopausal osteoporosis; disturbed parathyroid or thyroid function; major gastrointestinal disease (but not peptic diseases) or
Results
The initial characteristics of the study population are shown in Table 1. In none of the patients was baseline serum 25-hydroxy-vitamin D concentration lower than 12 ng/ml. All patients of the neridronate group completed the 36-month follow-up while four control patients did not show up at months 6, 18, and 24 because they preferred to initiate an active therapy for osteoporosis.
Neridronate was well tolerated. Thirteen percent of the patients developed clinical signs of an acute phase reaction
Discussion
Bimonthly IV administration of 50 mg neridronate results in significant suppression of biochemical markers of bone turnover and significant increases in BMD at both the spine and the hip. The order of changes in BMD are somewhat close to those reported after 1 year treatment with 10–20 mg/daily oral alendronate [14]. The BMD changes are also apparently superior to those obtained with other IV intermittent aminobisphosphonates. Thus, 4 mg/year zoledronate or 8 mg/year cumulative dose of
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