S. Ralston

FOCAL OSTEOMALACIA DUE TO LOW-DOSE DIPHOSPHONATE THERAPY IN PAGET'S DISEASE

Transiliac bone biopsies carried out on 13 patients with Pagets disease to evaluate the effects of low-dose diphosphonate (disodium etidronate) therapy showed focal osteomalacia in the 9 patients in whom post-therapy specimens were taken through pagetic bone. Active bone resorption persisted in 5 of these. A mineralisation defect not amounting to osteomalacia--ie, osteoid of increased thickness but of normal extent--was present in the 4 specimens taken through non-pagetic bone. Although 9 patients experienced symptomatic improvement, 2 suffered fissure fractures in affected lower limbs. In Pagets disease, the combination of osteomalacia and continuing active resorption within a lytic lesion may increase the risk of fracture in a weight-bearing bone. It is suggested that although disodium etidronate often provides effective pain relief it should be administered with caution until the optimum dose and duration of therapy are further evaluated.

Correlation of skeletal uptake of 99mTc-diphosphonate and alkaline phosphatase before and after oral diphosphonate therapy in Paget's disease

In Pagets disease of bone, quantitation of skeletal uptake of radiolabeled diphosphonate has been proposed as a means of monitoring response to therapy. However, the validity of such techniques has been questioned during oral diphosphonate therapy because of possible interaction between oral and radiolabeled diphosphonate. In the present study 18 patients with Pagets disease received a 6 month course of oral diphosphonate therapy. Measurements of 24 h whole body retention (WBR) of 99mTc-labeled hydroxyethylidene diphosphonate (HEDP), serum alkaline phosphatase (SAP), and urinary hydroxyproline excretion were obtained before, during, and after treatment. WBR correlated well with SAP and urinary hydroxyproline throughout the course of therapy. In addition, the relationship between WBR and SAP was maintained after cessation of oral diphosphonate. It would thus appear that in Pagets disease 24 h WBR of HEDP, a quantitative measure of skeletal uptake of diphosphonate, will reflect disease activity even in the presence of an oral diphosphonate load.

Factors predicting the acute effect of pamidronate on serum calcium in hypercalcemia of malignancy.

SummaryIn this study we retrospectively reviewed results of the first 9 days of treatment with pamidronate at doses of 30 mg (n=13), 45 mg (n=9), and 90 mg (n=13) in an attempt to see what factors influenced the response of serum calcium to pamidronate.The nadir of serum calcium obtained post treatment was correlated with pretreatment levels of nephrogenous cyclic adenosine monophosphate (NcAMP), the renal tubular threshold for phosphate reabsorption (TmPO4), and the renal tubular threshold for calcium reabsorption (TmCa). Using the post treatment serum calcium levels, patients were divided into “good” and “poor” responders depending on whether a normal serum calcium was obtained.Pretreatment NcAMP was significantly correlated with the magnitude of the response of serum calcium (r=0.45, P=0.0001). Pretreatment NcAMP was significantly higher in the poor responders (mean±SEM): 65.0±9.4 nmol/liter GF (poor responders) versus 29.6±6.3 (good responders), P=0.004. NcAMP as a predictor of the acute response of serum calcium showed a sensitivity of 93% and a specificity of 72%. Pretreatment TmPO4 was negatively correlated with the serum calcium response post treatment (r=-0.41, P=0.003). However, though TmPO4 tended to be lower in the poor responders, this was not statistically significant [0.65 mmol/liter GF±0.09 (poor responders) versus 0.76 mmol/liter GF±0.06 (good responders)]. As a predictor of the acute response of serum calcium, TmPO4 was less good with a sensitivity of 70% and specificity of 58%. No significant correlation was present between TmCa and the serum calcium response. A significant negative correlation was evident between NcAMP and TmPO4 (r=-0.35, P=0.003), however, no significant correlation was evident between NcAMP and TmCa or TmPO4 and TmCa.These results suggest that in a hypercalcemic patient where evidence exists for the presence in circulation of a factor with PTH-like activity (i.e., NcAMP is elevated or TmPO4 is low) the response of serum calcium to pamidronate is less good. NcAMP would appear to be a useful predictor of the response of serum calcium, whereas TmPO4 is less discriminating.