Near-infrared fluorescent probe traces bisphosphonate delivery and retention in vivo

Bisphosphonate use has expanded beyond traditional applications to include treatment of a variety of low-bone-mass conditions. Complications associated with long-term bisphosphonate treatment have been noted, generating a critical need for information describing the local bisphosphonate-cell interactions responsible for these observations. This study demonstrates that a fluorescent bisphosphonate analogue, far-red fluorescent pamidronate (FRFP), is an accurate biomarker of bisphosphonate deposition and retention in vivo and can be used to monitor site-specific local drug concentration. In vitro, FRFP is competitively inhibited from the surface of homogenized rat cortical bone by traditional bisphosphonates. In vivo, FRFP delivery to the skeleton is rapid, with fluorescence linearly correlated with bone surface area. Limb fluorescence increases linearly with injected dose of FRFP; injected FRFP does not interfere with binding of standard bisphosphonates at the doses used in this study. Long-term FRFP retention studies demonstrated that FRFP fluorescence decreases in conditions of normal bone turnover, whereas fluorescence was retained in conditions of reduced bone turnover, demonstrating preservation of local FRFP concentration. In the mandible, FRFP localized to the alveolar bone and bone surrounding the periodontal ligament and molar roots, consistent with findings of osteonecrosis of the jaw. These findings support a role for FRFP as an effective in vivo marker for bisphosphonate site-specific deposition, turnover, and long-term retention in the skeleton. © 2010 American Society for Bone and Mineral ResearchPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77952/1/66_ftp.pd

Bone marrow changes related to disuse

OBJECTIVE: To evaluate bone marrow changes on knee MRI in patients with 3-to-6 week long period of unloading. MATERIALS AND METHODS: MRI knee examinations were performed in 30 patients (14 men, 16 women, aged 20–53 years) at baseline and 5–10 weeks after immobilization of the ipsilateral lower extremity; subsets of patients were examined at additional time points. Ten volunteers (4 men, 6 women; aged 20–50) were studied as control cohort at 2 time points. Bone marrow signal abnormalities were analyzed according to 1) severity, 2) signal alteration relative to hyaline cartilage, 3) morphology, 4) increased vascularity in the knee joint and 5) T1-signal alteration. Spearman rank correlation test (SRC) and Kendall’s tau (KT) were used to compare individual scores. RESULTS: All 30 patients presented abnormal bone marrow findings after unloading, which reached a peak at 10–25 weeks (P <0.001). These findings decreased within one year (P <0.001). High scores of severity were associated with confluent and patchy patterns of bone marrow (SCR=0.923, P <0.01 and KT= 0.877 P <0.01). CONCLUSION: Signal abnormalities of the bone marrow related to unloading are consistent findings and most prominent 10–25 weeks following immobilization when both confluent and patchy hyperintense patterns are present

Bisphosphonate Treatment for Children With Disabling Conditions

Fractures are a frequent source of morbidity in children with disabling conditions. The assessment of bone density in this population is challenging, because densitometry is influenced by dynamic forces affecting the growing skeleton and may be further confounded by positioning difficulties and surgical hardware. First-line treatment for pediatric osteoporosis involves conservative measures, including optimizing the management of underlying conditions, maintaining appropriate calcium and vitamin D intake, encouraging weight-bearing physical activity, and monitoring measurements of bone mineral density. Bisphosphonates are a class of medications that increase bone mineral density by inhibiting bone resorption. Although bisphosphonates are commonly prescribed for treatment of adult osteoporosis, their use in pediatric patients is controversial because of the lack of long-term safety and efficacy data