Three Phase Bone Study

Schimmer R, Bauss F. Effect of daily and intermittent use of ibandronate on bone mass and bone turnover in postmenopausal osteoporosis a review of three phase II studies. Clin. Then, 2003, 25, 19-34. 

Three phase bone scanning requires that the symptomatic part of the patient be positioned under the gamma camera. Dynamic images of arterial flow are commenced simultaneously with the radiopharmaceutical administration. This enables assessment of arterial blood flow to the area under investigation. Subsequently, the blood pool and skeletal phases should then be accompanied as previously discussed for a two phase study. 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

Sideroblastic anemia is characterized by the accumulation of iron in the mitochondria of erythroblasts. In a Phase I study in 35 patients with refractory tumors, eight taking CMT-3 developed anemia without leukopenia or thrombocytopenia (54). Three of these patients underwent bone-marrow examination and each had ringed side-roblasts. The authors referred to several cases of aplastic anemia, megaloblastic anemia, and hemolytic anemia in which members of the tetracycline family have been implicated. However, they stated that there has been no previous reports of sideroblastic anemia associated with any tetracycline derivative and that the molecular mechanisms by which CMT-3 might cause sideroblastic anemia are unclear. 

It would seem that X-ray diffraction or electron microscopic studies of the bone minerals could help in describing the mineral phase of the bone. Unfortunately, specialists do not agree on a uniform description of the crystal morphology of bone. At least three different interpretations of the observations made by X-ray diffraction or by electron microscopy prevail. A brief outline of the three theories is presented. On the basis of electron microscopic examination, the mineral phase of bone is described as a honeycombed mineral framework. The organic substance is enclosed... 

---