Evaluation of biodistribution by local versus systemic administration of 99mTc-labeled pamidronate

Background: There is an emerging interest in utilizing local and systemic administration of bisphosphonates in orthopedics. The primary objective of this study was to use 99mTcpamidronate (99mTc-PAM) as a tool and compare bone and tissue uptake by local versus systemic administration. Methods: 99mTc-PAM was administered intravenously (i.v.), subcutaneously (s.c.) and by direct application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The animals were imaged at 2h and 24h after administration and then killed. Organs were harvested, and their radioactivity was estimated. Specific uptake in the right femur was compared between groups, as was systemic exposure to 99mTc PAM. Results: Bone uptake of 99mTc-PAM in the i.v. and s.c. groups was 2.2 ± 0.15 and 0.65 ± 0.07% ID/g, respectively, at the 2h time point. Uptake by surgically exposed right femur (d.a) was 5.15 ± 0.26% ID/g, 134% higher than the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone when the femur was fractured (d.a.#f), the uptake was 7.89 ± 0.46% ID/g, a further 50% increase (P < 0.05). The uptake of 99mTc-PAM increased after 24h of application to 2.4 ± 0.15, 1.53 ± 0.09, 7.94 ± 0.99, and 13.2 ± 0.80% ID/g) for i.v., s.c., d.a., and d.a.#f methods, respectively. The increases in uptake for the d.a. methods were significantly higher than for the local methods at the 24-h time point (P < 0.05). Although renal uptake was comparable with the i.v. and s.c. methods (0.22 ± 0.03 and 0.22 ± 0.04% ID/g), it was significantly lower with the d.a. methods (0.05 ± 0.07 and 0.16 ± 0.07% ID/g) (P < 0.05). The corresponding urinary excretion was 55%, 45%, 36%, and 35% of the injected dose at 24 h. Conclusions: The results indicate that the bone uptake of 99mTc-PAM was significantly higher (P = 0.001) and the kidney uptake significantly lower (P = 0.004) with the d.a. methods than with the i.v. or s.c. method. The findings indicate the need for further study into the potential of local administration of bisphosphonates in the presence of orthopedic indications.9 page(s

Bone mineral density in adolescent female athletes: relationship to exercise type and muscle strength

Purpose: This study investigated the influence of different exercise types and differences in anatomical distribution of mechanical loading patterns on bone mineral density (BMD) in elite female cyclists, runners, swimmers, triathletes, and controls (N = 15 per group). Associations between leg strength and BMD were also examined. Methods: Areal BMD (g·cm−2) was assessed by duel-energy x-ray absorptiometry (DXA) (total body (TB), lumbar spine (LS), femoral neck (FN), legs, and arms). Right knee flexion and extension strength was measured using a Cybex Norm isokinetic dynamometer at 60°·s−1. Results: Runners had significantly higher unadjusted TB, LS, FN, and leg BMD than controls (P < 0.05); higher TB, FN, and leg BMD than swimmers (P < 0.05); and greater leg BMD than cyclists (P < 0.05). Absolute knee extension strength was significantly (P < 0.01) correlated (0.33 ≤ r ≤ 0.44) with TB, FN, LS, and leg BMD for all groups combined. Weaker but still significant correlations (0.28 ≤ r ≤ 0.33) existed for normalized (per leg lean tissue mass) knee extension strength and all BMD sites, except FN BMD. There were no significant correlations between absolute or normalized knee flexion strength and any of the BMD variables. Absolute knee extension strength was entered as the second independent predictor for LS and leg BMD in stepwise multiple linear regression analysis (MLRA), accounting for increments of 4% and 12%, respectively, in total explained variation. Conclusion: We conclude that running, a weight bearing exercise, is associated with larger site-specific BMD than swimming or cycling, that the generalized anatomical distribution of loads in triathlon appears not to significantly enhance total body BMD status, and that knee extension strength is only a weak correlate and independent predictor of BMD in adolescent females