Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis

Dosing convenience is a key element in the effective management of any chro nic disease, and is particularly important in the long-term management of o steoporosis. Less frequent dosing with any medication may enhance complianc e, thereby maximizing the effectiveness of therapy. Animal data support the rationale that once-weekly dosing with alendronate 70 mg (7 times the dail y oral treatment dose) could provide similar efficacy to daily dosing with alendronate 10 mg due to its long duration of effect in bone. In addition, dog studies suggest that the potential for esophageal irritation, observed with daily oral bisphosphonates, may be substantially reduced with once-wee kly dosing. This dosing regimen would provide patients with increased conve nience and would be likely to enhance patient compliance. We compared the e fficacy and safety of treatment with oral once-weekly alendronate 70 mg (N= 519), twice-weekly alendronate 35 mg (N=369), and dal ly alendronate 10 mg (N=370) in a one-year, double-blind, multicenter study of postmenopausal wo men (ages 42 to 95) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak premenopausal mea n, or prior vertebral or hip fracture). The primary efficacy endpoint was t he comparability of increases in lumbar spine BMD, using strict pre-defined equivalence criteria. Secondary endpoints included changes in BMD at the h ip and total body and rate of bone turnover, as assessed by biochemical mar kers. Both of the new regimens fully satisfied the equivalence criteria rel ative to daily therapy. Mean increases in lumbar spine BMD at 12 months wer e: 5.1% (95% CI 4.8, 5.4) in the 70 mg once-weekly group, 5.2% (4.9, 5.6) i n the 35 mg twice-weekly group, and 5.4% (5.0, 5.8) in the 10 mg daily trea tment group. Increases in BMD at the total hip, femoral neck, trochanter, a nd total body were similar for the three dosing regimens. All three treatme nt groups similarly reduced biochemical markers of bone resorption (urinary N-telopeptides of type I collagen) and bone formation (serum bone-specific alkaline phosphatase) into the middle of the premenopausal reference range . All treatment regimens were well tolerated with a similar incidence of up per GI adverse experiences. There were fewer serious upper GI adverse exper iences and a trend toward a lower incidence of esophageal events in the onc e-weekly dosing group compared to the daily dosing group. These data are co nsistent with preclinical animal models, and suggest that once-weekly dosin g has the potential for improved upper GI tolerability. Clinical fractures, captured as adverse experiences, were similar among the groups. We conclud e that the alendronate 70 mg once-weekly dosing regimen will provide patien ts with a more convenient, therapeutically equivalent alternative to daily dosing, and may enhance compliance and long-term persistence with therapy. (Aging Clin. Exp. Res. 12: 1-12, 2000) (C)2000, Editrice Kurtis.