Effects of teriparatide, alendronate, or both on bone turnover in osteoporotic men

Context: We have previously demonstrated that alendronate reduces the ability of teriparatide to increase bone mineral density (BMD) in osteoporotic men. The underlying basis for this observation is poorly understood. Objective: The primary aim of this study was to determine whether teriparatide increases osteoblast activity when the ability of teriparatide to increase osteoclast activity is suppressed by alendronate. Design: This was a nonblinded, randomized, controlled trial. Setting: The study was conducted at the General Clinical Research Center of a teaching hospital. Patients: We studied 63 men, age 46-85, with low spine and/or hip BMD. Interventions: Subjects received alendronate 10 mg daily (group 1), teriparatide 37 mu g sc daily (group 2), or both (group 3) for 30 months. Teriparatide was begun at month 6. Main Outcome Measures: The primary endpoint was the change in serum N-telopeptide, osteocalcin, and amino-terminal propeptide of type 1 procollagen. Results: In men receiving teriparatide monotherapy (group 2), levels of all bone turnover markers increased markedly during the first 6 months of teriparatide administration and then declined toward baseline during the next 18 months. In men who received combination therapy (group 3), bone turnover marker levels declined in the first 6 months (while receiving alendronate alone) and then returned to baseline levels (N-telopeptide) or above (osteocalcin and aminoterminal propeptide of type 1 procollagen) after teriparatide was added. Changes in each marker were significantly different between groups 1 and 2 (all P values < 0.001), groups 1 and 3 (all P values < 0.001), and groups 2 and 3 ( all P values < 0.03). Conclusions: As with BMD, alendronate impairs the action of teriparatide to increase bone turnover in men.