Bisphosphonate space measurement and dosage requirement for intravenous clodronate treatment of Paget's disease.

It has been claimed that the bisphosphonate space, a scintigraphic technique which simultaneously estimates bone uptake and renal clearance of bisphosphonate, can be used to predict the dose of bisphosphonate required to induce biochemical remission in Paget's disease. In a prospective study of 15 newly diagnosed patients with Paget's disease, bisphosphonate space measurements were made prior to treatment with intravenous clodronate. Treatment with clodronate 0.6 g was given four times weekly until the alkaline phosphatase (ALP) suppressed below the upper level of the reference range (120 u/l) or reached a plateau, and the cumulative dose required (1.8-7.8 g) was calculated. Overall, the bisphosphonate space correlated poorly with the total dose requirement (r = 0.441, P = 0.100), but the relationship was weakened by an outlier, who had the poorest renal function. Excluding this subject improved the correlation coefficient (r = 0.852, P <0.0001). The relationship between dose requirement and log10 initial ALP was not as strong (r = 0.672, P <0.01). However, for both ALP and the bisphosphonate space the 95% prediction intervals were wide. We conclude that the bisphosphonate space does relate to dose requirements for intravenous bisphosphonates, but that it is unreliable when renal function is poor, and may not offer much gain over the pretreatment ALP levels. Both ALP and the bisphosphonate space have wide prediction intervals, and are therefore poor guides to dose requirement.