Intravenous Zoledronic Acid in Postmenopausal Women With Low Bone Mineral Density

Abstract

Background Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored. MethodsWe studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at threemonth intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point. ResultsThere were similar increases in bone mineral density in all the zoledronic acid groups to values for the spine that were 4.3 to 5.1 percent higher than those in the placebo group (P<0.001) and values for the femoral neck that were 3.1 to 3.5 percent higher than those in the placebo group (P<0.001). Biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups. Myalgia and pyrexia occurred more commonly in the zoledronic acid groups, but treatment-related dropout rates were similar to that in the placebo group.Conclusions Zoledronic acid infusions given at intervals of up to one year produce effects on bone turnover and bone density as great as those achieved with daily oral dosing with bisphosphonates with proven efficacy against fractures, suggesting that an annual infusion of zoledronic acid might be an effective treatment for postmenopausal osteoporosis.

Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws

“…Ninety-four percent of patients with osteonecrosis received pamidronate or zoledronic acid. The doses for oncologic indications are often up to 12 times higher than those used for osteoporosis (13,59). Of interest, clodronate, a nonaminobisphosphonate, has not been implicated in the development of osteonecrosis (60).…”

Prolonged antiresorptive activity of zoledronate: A randomized, controlled trial

“…At the conclusion of the 12-month trial period, bone turnover markers in the group that received a single 4-mg dose of zoledronate at baseline were substantially lower than those in the placebo group. (3) In randomized, placebo-controlled trials of men with HIV infection (4) and osteopenic postmenopausal women, (5) antiresorptive activity was apparent 24 months after the second of two annual 4-mg doses of zoledronate and a single 5-mg baseline dose, respectively, suggesting a duration of action considerably beyond 12 months.…”

Efeito do ácido zoledrônico em tíbias de ratas ooforectomizadas: estudo prospectivo e randomizado

“…Após o climatério, em função da alteração não apenas da distribuição de tecido adiposo, causado pela deficiência de estrógenos, mas também pelo acú-mulo periférico de gordura, ocorre alteração do perfil lipídico e aumento da massa corporal (31) . Não verificamos, neste estudo, a influência do ácido zoledrônico no aumento da massa corporal dos animais, fato também comprovado por Reid et al (16) , Hornby et al (32) , Otrock et al (33) e Gilfillan et al (34) . Conclui-se, portanto, que o aumento da massa corpórea foi causado pela retirada dos ovários (ooforectomia) e não pelas substâncias administradas.…”

“…O ácido zoledrônico (zoledronato), um novo bisfosfonato, na dose de 5mg ao ano, em infusão endovenosa, é indicado como capaz de diminuir os efeitos colaterais decorrentes do uso diário desta classe farmacológica, bem como eliminar a baixa adesão dos pacientes ao tratamento (15,16) .…”