Purpose: Receptor activator of nuclear factor-nB ligand (RANKL) is essential for the differentiation, function, and survival of osteoclasts, which play a key role in establishment and propagation of skeletal disease in patients with multiple myeloma or bone metastases as well as many other skeletal diseases. Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, was developed to treat patients with skeletal diseases. Experimental Design: This was a randomized, double-blind, double-dummy, active-controlled, multicenter study to determine the safety and efficacy of denosumab in patients with breast cancer (n = 29) or multiple myeloma (n = 25) with radiologically confirmed bone lesions. Patients received a single dose of either denosumab (0.1, 0.3, 1.0, or 3.0 mg/kg s.c.) or pamidronate (90 mg i.v.). Bone antiresorptive effect was assessed by changes in urinary and serum N-telopeptide levels. Pharmacokinetics of denosumab also were assessed. Results: Following a single s.c. dose of denosumab, levels of urinary and serum N-telopeptide decreased within 1day, and this decrease lasted through 84 days at the higher denosumab doses. Pamidronate also decreased bone turnover, but the effect diminished progressively through follow-up. Denosumab injections were well tolerated. Mean half-lives of denosumab were 33.3 and 46.3 days for the two highest dosages. Conclusions: A single s.c. dose of denosumab given to patients with multiple myeloma or bone metastases from breast cancer was well tolerated and reduced bone resorption for at least 84 days. The decrease in bone turnover markers was similar in magnitude but more sustained than with i.v. pamidronate.The propensity of breast cancer cells to metastasize and proliferate in bone is currently explained by a ''seed and soil'' concept (1, 2). Once breast cancer cells colonize the bone marrow, they are attracted to bone surfaces by products of resorbing bone and destroy bone via osteoclast stimulation. The importance of direct osteolytic effects of metastatic cancer cells, including the effects of collagenases, remains uncertain. Breast cancer cells (the ''seed'') seem to secrete factors, such as parathyroid hormone-related protein, that potentiate the development of metastases in the skeleton, which constitutes a fertile ''soil'' rich in cytokines and growth factors that stimulate growth of breast cancer cells. Osteoclasts arise from precursor cells in the monocyte-macrophage lineage. Several osteoclastogenic factors have been implicated in the increased recruitment and activity of osteoclasts in myeloma (3). Active osteoclasts are found in proximity to tumor cells (4) and play a key role in bone lysis in patients with multiple myeloma or cancer-related bone metastases. Normal homeostatic mechanisms are unable to control osteoclastic bone resorption in this setting and the bone destruction often leads to dramatic complications, such as pathologic vertebral and long-bone fractures, pain requiring radiotherapy, spinal cord compression, and hypercalcemia (5).Desp...

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Aim: to determine how collecting urine voided directly into a container compares with urine obtained by suprapubic aspiration. Method: urine samples were collected in a sterile recipient placed in the toilet or in the bed-pan during voiding, after the vulval region had been cleaned by water. These samples were compared with samples of the same urine obtained by suprapubic aspiration. The samples were examined for pyuria and bacteriuria. Applying the Kass criteria on the voided urine specimen and assessing the presence of leucocyturia, it was possible to differentiate urinary tract infection, asymptomatic bacteriuria and contamination. Results: all 13 cases of infection found on suprapubic aspiration were also identified by this sampling technique. The technique produced four false-positive results. Conclusion: this simple sampling method may not only obviate the need for suprapubic aspiration but also for bladder catheterization in the diagnosis of urinary tract infection in many elderly women.

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