Intramuscular neridronate in postmenopausal women with low bone mineral density.

Compliance to osteoporosis treatment with oral bisphosphonates is very poor. Intermittent intravenous bisphosphonate is a useful alternative, but this route is not readily available. Neridronate, a nitrogen-containing bisphosphonate that can be given intramuscularly (IM), was tested in a phase 2 clinical trial in 188 postmenopausal osteoporotic women randomized to IM treatment with 25 mg neridronate every 2 weeks, neridronate 12.5 or 25 mg every 4 weeks, or placebo. All patients received calcium and vitamin D supplements. The patients were treated over 12 months with 2-year posttreatment follow-up. After 12-month treatment, all three doses were associated with significant bone mineral density (BMD) increases at both the total hip and spine. A significant dose-response relationship over the three doses was observed for the BMD changes at the total hip but not at the spine. Bone alkaline phosphatase decreased significantly by 40-55% in neridronate-treated patients, with an insignificant dose-response relationship. Serum type I collagen C-telopeptide decreased by 58-79%, with a significant dose-response relationship (P < 0.05). Two years after treatment discontinuation, BMD declined by 1-2% in each dose group, with values still significantly higher than baseline at both the spine and the total hip. Bone turnover markers progressively increased after treatment discontinuation, and on the second year of follow-up the values were significantly higher than pretreatment baseline. The results of this study indicate that IM neridronate might be of value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusion of bisphosphonates.

Intravenous neridronate for skeletal damage treatment in patients with multiple myeloma.

Almost 70-80% of the patients with Multiple Myeloma (MM) in advancer phase, of the disease show osteolytic lesions and/or pathologic fractures, with or without secondary osteoporosis. An accelerated osteoclast-mediated bone absorption is believed to be the main cause of bone damage in MM. Osteoclast can be activated by a variety of microenvironmental factors. Bisphosphonates (BF) induce the apoptosis of osteoclasts and inhibit osteoclastogenesis, thus preventing bone absorption. As well as BFs, the so-called second-generation BF (N-BF) may impair the activity of osteoclast. Neridronic acid (NER) is a N-BF molecule officially registered for the treatment of osteogenesis imperfecta. Nevertheless, NER has shown a remarkable efficacy in Paget's disease, postmenopausal osteoporosis and, most recently, in androgen deprivation-treated prostatic carcinoma. The primary endpoint of this study was to evaluate hip and spine Bone Mineral Density (BMD) modifications over the 12-month treatment with NER in a group of patients affected by MM with evidence of initial skeletal damage. Secondary endpoints were (1) changes of calcium and total Alkaline Phosphatase (tAP) plasma levels during treatment with NER and (2) tolerability of 100 mg NER monthly administration for 12 months. These data suggest that NER, if administered at these doses and timing, might allow at least for one year sustained BMD increases in patients. NER has been highly tolerated in this study. The almost complete absence of adverse effects has prompted us to reduce the time of infusions at the end of the study. In conclusion, this study provides the first data on the efficacy and safety of NER in patients with MM-induced bone damage. These initial data encourage wider phase III trials to clearly assess its efficacy in preventing skeletal-related events and its possible anti-neoplastic properties.