Effect of treatment with calcitriol combined with low-dosage alendronate in involutional osteoporosis

Background: The window of efficacy for calcitriol is quite narrow: 0.5 mu g /day is effective in most patients, but sometimes higher dosages are necess ary to provide increases in bone mass. Combined treatment with calcitriol a nd an anti-resorptive agent may be useful when calcitriol 0.5 mu g/day is n ot entirely effective and higher dosages cannot be used because of toxicity . Objective: To evaluate the metabolic changes and the effects on bone densit y of combined treatment with calcitriol and a low dosage of alendronate (al endronic acid) in osteoporotic women who had failed to respond to calcitrio l treatment alone. Design and Setting: This was a nonblind, prospective study of outpatients r ecruited by the Metabolic Bone Disease Center of the University of Siena, I taly. Patients and Participants: The study involved 30 women aged 54 to 74 years with established involutional osteoporosis. Interventions: Calcitriol 0.5 mu g/day was administered orally for 2 years. During the second year of the trial, cyclic treatment with alendronate 10 mg/day (2 months on, 2 months off) was added in 12 patients in whom bone mi neral density (BMD) was unchanged or decreased. Main Outcome Measures: BMD of whole skeleton and single anatomical areas wa s measured by dual-energy X-ray absorptiometry at baseline and after 12 and 24 months, together with serum and urinary calcium, serum and urinary phos phate, serum alkaline phosphatase, serum creatinine and urinary hydroxyprol ine. Results: In 18 osteoporotic women treated continuously for 2 years with cal citriol, the total BMD increased significantly (p < 0.001) after 12 (1.45%) and 24 (2.04%) months; a similar trend was also observed for spine BMD (0. 67% after 12 months, 0.36% after 24 months). Calcitriol therapy for 1 year did not increase total (-1.27%, p < 0.001) and spine (-0.47%) BMD in 12 pat ients; the addition of a low dosage of alendronate for 12 months reversed B MD values (total body: 0.86%, p < 0.01; spine 3.23%, p < 0.001). The increa se in urinary calcium was less marked in patients treated with calcitriol p lus alendronate. No adverse effects were observed during the 2 years of the study, in particular with respect to renal function and the digestive trac t. Conclusions: These data demonstrate the efficacy and tolerability of combin ed treatment with calcitriol plus a low dosage of alendronate in women with involutional osteoporosis, and support the rationale of the addition of an anti-resorptive agent whenever the response to calcitriol is unsatisfactor y.