Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005940 (bone disease)
 7,459 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the study of parathyroid function in 19 hemodialysis patients with low turnover aluminum bone disease, it was observed that serum parathyroid hormone (PTH) levels were higher during the induction of hypocalcemia than during the recovery from hypocalcemia. This type of PTH response has been termed hysteresis. Hypocalcemia was induced during hemodialysis with a calcium-free dialysate. When the total serum calcium level decreased to 7 mg/dL, the dialysate calcium concentration was changed to 3.5 mEq/L and the dialysis session was completed. One week later, hypercalcemia was induced during hemodialysis with a high-calcium dialysate. The mean basal PTH level was 132 +/- 37 pg/mL (normal, 10 to 65 pg/mL; immunoradiometric (IRMA), Nichols Institute, San Juan Capistrano, CA) and increased to a maximal PTH level of 387 +/- 91 pg/mL during hypocalcemia. For the same ionized calcium concentration, the PTH level was higher during the induction of hypocalcemia than during the recovery from hypocalcemia. Conversely, for the same ionized calcium concentration, the PTH level was greater when hypercalcemia was induced from the nadir of hypocalcemia than when hypercalcemia was induced from basal serum calcium. The set point of calcium (defined as the serum calcium concentration required to reduce maximal PTH by 50%) was greater during the induction of hypocalcemia than during the recovery from hypocalcemia (4.44 +/- 0.10 versus 4.25 +/- 0.09 mg/dL; P = 0.03). The mean basal ionized calcium concentration and the mean ionized calcium concentration at the intersection of the two PTH-calcium curves were the same (4.61 +/- 0.13 versus 4.61 +/- 0.12 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hysteresis of the parathyroid hormone response to hypocalcemia in hemodialysis patients with low turnover aluminum bone disease. 177 94

Recent advances in adjuvant treatment have improved progression-free and overall survival in patients with early stage breast cancer. However, up to one third of women will experience tumour recurrence, with bone being a common metastatic site. Current treatment options for metastases to bone comprise systemic antitumour therapy, irradiation, surgery and biphosphonates. As osteoclast activation is mediated by the receptor activator of NF-kappaB (RANK)/RANK ligand pathway and inhibited by osteoprotegerin (OPG), it was suggested that inhibition of this system may treat bone metastases. Recombinant Fc-OPG was evaluated in women with osteoporosis and malignant bone disease. The fully human antibody denosumab has demonstrated superior activity in reducing markers of bone turnover; therefore this drug was further developed in clinical settings. In advanced breast cancer, denosumab reduced urinary-N-telopeptide:creatinine ratio with potentially fewer side effects compared with bisphosphonates. Proof of direct antitumor activity is missing. Here we review the development and current status of denosumab in breast cancer. Data were obtained by searching the Medline database and abstracts from the American Society for Clinical Oncology (ASCO) annual meeting, European Cancer organization (ECCO), European Society for Medical Oncology (ESMO) and the San Antonio Breast Cancer Symposium, using search terms including bone metastases, bisphosphonates, breast cancer, denosumab, osteoprotegerin, RANK and skeletal-related events.
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PMID:Role of denosumab in breast cancer. 1965 67

Bone metastases are a common occurrence in several malignancies, including breast, prostate, and lung. Once established in bone, tumors are responsible for significant morbidity and mortality. Thus, there is a significant need to understand the molecular mechanisms controlling the establishment, growth and activity of tumors in bone. Several in vivo models have been established to study these events and each has specific benefits and limitations. The most commonly used model utilizes intracardiac inoculation of tumor cells directly into the arterial blood supply of athymic (nude) BalbC mice. This procedure can be applied to many different tumor types (including PC-3 prostate cancer, lung carcinoma, and mouse mammary fat pad tumors); however, in this manuscript we will focus on the breast cancer model, MDA-MB-231. In this model we utilize a highly bone-selective clone, originally derived in Dr. Mundy's group in San Antonio, that has since been transfected for GFP expression and re-cloned by our group. This clone is a bone metastatic variant with a high rate of osteotropism and very little metastasis to lung, liver, or adrenal glands. While intracardiac injections are most commonly used for studies of bone metastasis, in certain instances intratibial or mammary fat pad injections are more appropriate. Intracardiac injections are typically performed when using human tumor cells with the goal of monitoring later stages of metastasis, specifically the ability of cancer cells to arrest in bone, survive, proliferate, and establish tumors that develop into cancer-induced bone disease. Intratibial injections are performed if focusing on the relationship of cancer cells and bone after a tumor has metastasized to bone, which correlates roughly to established metastatic bone disease. Neither of these models recapitulates early steps in the metastatic process prior to embolism and entry of tumor cells into the circulation. If monitoring primary tumor growth or metastasis from the primary site to bone, then mammary fat pad inoculations are usually preferred; however, very few tumor cell lines will consistently metastasize to bone from the primary site, with 4T1 bone-preferential clones, a mouse mammary carcinoma, being the exception. This manuscript details inoculation procedures and highlights key steps in post inoculation analyses. Specifically, it includes cell culture, tumor cell inoculation procedures for intracardiac and intratibial inoculations, as well as brief information regarding weekly monitoring by x-ray, fluorescence and histomorphometric analyses.
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PMID:Models of bone metastasis. 2297 96

The 9th Bone and the Oncologist New Updates conference was held in Ottawa, Canada during 2014. This annual meeting focuses on innovative research into the mechanisms and consequences of treatment-induced and metastatic bone disease. Given the recent presentation of the Oxford overview's "Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: A meta-analysis of individual patient data from randomized trials" at the San Antonio Breast Cancer Symposium, a debate as to the pro's and con's of adjuvant bisphosphonate use in early stage breast cancer was undertaken. As bisphosphonate treatment in post-menopausal women appeared to demonstrate a similar magnitude of benefit to that of other commonly used adjuvant strategies the debate assessed whether or not there was sufficient data to incorporate adjuvant bisphosphonates into standard practice and if so, in which patient populations.
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PMID:Are adjuvant bisphosphonates now standard of care of women with early stage breast cancer? A debate from the Canadian Bone and the Oncologist New Updates meeting. 2657 89